Pub Date : 2024-01-01Epub Date: 2023-11-21DOI: 10.1007/s00441-023-03841-y
Sanjiv Neupane, Yam Prasad Aryal, Hee-Jin Kwak, Sung-Gwon Lee, Tae-Young Kim, Elina Pokharel, Ji-Youn Kim, Jung-Hyeuk Kim, Wern-Joo Sohn, Seo-Young An, Chang-Hyeon An, Jae-Kwang Jung, Jung-Hong Ha, Hitoshi Yamamoto, Sung-Won Cho, Sanggyu Lee, Youngkyun Lee, Kwang-Kyun Park, Bong-Ki Min, Chungoo Park, Tae-Yub Kwon, Sung-Jin Cho, Jae-Young Kim
Glomerular epithelial protein-1 (Glepp1), a R3 subtype family of receptor-type protein tyrosine phosphatases, plays important role in the activation of Src family kinases and regulates cellular processes such as cell proliferation, differentiation, and apoptosis. In this study, we firstly examined the functional evaluation of Glepp1 in tooth development and morphogenesis. The precise expression level and developmental function of Glepp1 were examined by RT-qPCR, in situ hybridization, and loss and gain of functional study using a range of in vitro organ cultivation methods. Expression of Glepp1 was detected in the developing tooth germs in cap and bell stage of tooth development. Knocking down Glepp1 at E13 for 2 days showed the altered expression levels of tooth development-related signaling molecules, including Bmps, Dspp, Fgf4, Lef1, and Shh. Moreover, transient knock down of Glepp1 revealed alterations in cellular physiology, examined by the localization patterns of Ki67 and E-cadherin. Similarly, knocking down of Glepp1 showed disrupted enamel rod and interrod formation in 3-week renal transplanted teeth. In addition, due to attrition of odontoblastic layers, the expression signals of Dspp and the localization of NESTIN were almost not detected after knock down of Glepp1; however, their expressions were increased after Glepp1 overexpression. Thus, our results suggested that Glepp1 plays modulating roles during odontogenesis by regulating the expression levels of signaling molecules and cellular events to achieve the proper structural formation of hard tissue matrices in mice molar development.
{"title":"Developmental roles of glomerular epithelial protein-1 in mice molar morphogenesis.","authors":"Sanjiv Neupane, Yam Prasad Aryal, Hee-Jin Kwak, Sung-Gwon Lee, Tae-Young Kim, Elina Pokharel, Ji-Youn Kim, Jung-Hyeuk Kim, Wern-Joo Sohn, Seo-Young An, Chang-Hyeon An, Jae-Kwang Jung, Jung-Hong Ha, Hitoshi Yamamoto, Sung-Won Cho, Sanggyu Lee, Youngkyun Lee, Kwang-Kyun Park, Bong-Ki Min, Chungoo Park, Tae-Yub Kwon, Sung-Jin Cho, Jae-Young Kim","doi":"10.1007/s00441-023-03841-y","DOIUrl":"10.1007/s00441-023-03841-y","url":null,"abstract":"<p><p>Glomerular epithelial protein-1 (Glepp1), a R3 subtype family of receptor-type protein tyrosine phosphatases, plays important role in the activation of Src family kinases and regulates cellular processes such as cell proliferation, differentiation, and apoptosis. In this study, we firstly examined the functional evaluation of Glepp1 in tooth development and morphogenesis. The precise expression level and developmental function of Glepp1 were examined by RT-qPCR, in situ hybridization, and loss and gain of functional study using a range of in vitro organ cultivation methods. Expression of Glepp1 was detected in the developing tooth germs in cap and bell stage of tooth development. Knocking down Glepp1 at E13 for 2 days showed the altered expression levels of tooth development-related signaling molecules, including Bmps, Dspp, Fgf4, Lef1, and Shh. Moreover, transient knock down of Glepp1 revealed alterations in cellular physiology, examined by the localization patterns of Ki67 and E-cadherin. Similarly, knocking down of Glepp1 showed disrupted enamel rod and interrod formation in 3-week renal transplanted teeth. In addition, due to attrition of odontoblastic layers, the expression signals of Dspp and the localization of NESTIN were almost not detected after knock down of Glepp1; however, their expressions were increased after Glepp1 overexpression. Thus, our results suggested that Glepp1 plays modulating roles during odontogenesis by regulating the expression levels of signaling molecules and cellular events to achieve the proper structural formation of hard tissue matrices in mice molar development.</p>","PeriodicalId":9712,"journal":{"name":"Cell and Tissue Research","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138175724","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-01Epub Date: 2023-12-05DOI: 10.1007/s00441-023-03848-5
Pinar Calis, Gokcenur Arik, Cemile Merve Seymen, Gokce Kaynak Bayrak, Ozge Ekin Akdere, Canan Yilmaz, Atiye Seda Yar Saglam, Menemşe Gümüşderelioğlu, Gulnur Take Kaplanoglu
Premature ovarian insufficiency (POI) is defined as the development of hypergonadotropic hypogonadism before the age of 40 with definitive treatment being absent. In the current study, we aim to compare the efficacy of the cell sheet method with an intravenous (IV) application of adipose-derived mesenchymal stem cells (AdMSCs) to the POI with an animal model. In the current prospective study, 6-to-8-week-old Sprague Dawley rats were generated four groups: (i) a control group in which only PBS was administered; (ii) an only-POI group generated by cyclophosphamide; (iii) a POI group treated by way of IV AdMSCs; and (iv) a POI group treated by way of the cell sheet method. Twenty-eight days after an oophorectomy was performed, intracardiac blood was taken. Follicle count, immunohistochemical examination for GDF9, BMP15, and TUNEL were conducted, gene expressions of GDF9 and BMP15 were examined, and E2 was measured in the serum samples. With hematoxylin-eosin, in the third group, multi oocytes follicles were the most remarkable finding. In the fourth group, most of the follicles presented normal morphology. GDF9 involvement was similar between the first and fourth groups. BMP-15 immunoreactivity, in contrast to fourth group, was weak in all stages in the second and third groups. The current attempt represents a pioneer study in the literature in which a cell sheet method is used for the first time in a POI model. These results suggest that the cell sheet method may be a feasible and efficient method for the stem cell treatment of models with POI and could be a new treatment approach in POI.
{"title":"A new technology for the treatment of premature ovarian insufficiency: Cell sheet.","authors":"Pinar Calis, Gokcenur Arik, Cemile Merve Seymen, Gokce Kaynak Bayrak, Ozge Ekin Akdere, Canan Yilmaz, Atiye Seda Yar Saglam, Menemşe Gümüşderelioğlu, Gulnur Take Kaplanoglu","doi":"10.1007/s00441-023-03848-5","DOIUrl":"10.1007/s00441-023-03848-5","url":null,"abstract":"<p><p>Premature ovarian insufficiency (POI) is defined as the development of hypergonadotropic hypogonadism before the age of 40 with definitive treatment being absent. In the current study, we aim to compare the efficacy of the cell sheet method with an intravenous (IV) application of adipose-derived mesenchymal stem cells (AdMSCs) to the POI with an animal model. In the current prospective study, 6-to-8-week-old Sprague Dawley rats were generated four groups: (i) a control group in which only PBS was administered; (ii) an only-POI group generated by cyclophosphamide; (iii) a POI group treated by way of IV AdMSCs; and (iv) a POI group treated by way of the cell sheet method. Twenty-eight days after an oophorectomy was performed, intracardiac blood was taken. Follicle count, immunohistochemical examination for GDF9, BMP15, and TUNEL were conducted, gene expressions of GDF9 and BMP15 were examined, and E2 was measured in the serum samples. With hematoxylin-eosin, in the third group, multi oocytes follicles were the most remarkable finding. In the fourth group, most of the follicles presented normal morphology. GDF9 involvement was similar between the first and fourth groups. BMP-15 immunoreactivity, in contrast to fourth group, was weak in all stages in the second and third groups. The current attempt represents a pioneer study in the literature in which a cell sheet method is used for the first time in a POI model. These results suggest that the cell sheet method may be a feasible and efficient method for the stem cell treatment of models with POI and could be a new treatment approach in POI.</p>","PeriodicalId":9712,"journal":{"name":"Cell and Tissue Research","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138482064","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Peripheral artery disease (PAD) affects more than 230 million people worldwide, with approximately 11% of patients presenting with advanced-stage PAD or critical limb ischemia (CLI). To avoid or delay amputation, particularly in no-option CLI patients with infeasible or ineffective revascularization, new treatment strategies such as regenerative therapies should be developed. Mesenchymal stem cells (MSCs) are the most popular cell source in regenerative therapies. They possess significant characteristics such as angiogenic, anti-inflammatory, and immunomodulatory activities, which encourage their application in different diseases. This phase I clinical trial reports the safety, feasibility, and probable efficacy of the intramuscular administration of allogeneic Wharton’s jelly-derived MSCs (WJ-MSCs) in type 2 diabetes patients with CLI. Out of six screened patients with CLI, five patients were administered WJ-MSCs into the gastrocnemius, soleus, and the proximal part of the tibialis anterior muscles of the ischemic lower limb. The safety of WJ-MSCs injection was considered a primary outcome. Secondary endpoints included wound healing, the presence of pulse at the disease site, the absence of amputation, and improvement in visual analogue scale (VAS), pain-free walking time, and foot and ankle disability index (FADI). No patient experienced adverse events and foot or even toe amputation during the 6-month follow-up. Six months after the intervention, there were a significantly lower VAS score and significantly higher pain-free walking time and FADI score than the baseline, but no statistically significant difference was seen between other time points. In conclusion, allogeneic WJ-MSC transplantation in patients with CLI seems to be safe and effective.
全世界有超过 2.3 亿人患有外周动脉疾病(PAD),其中约 11% 的患者为晚期 PAD 或危重肢体缺血(CLI)。为了避免或推迟截肢,特别是对于无法选择血管再通或血管再通效果不佳的危重肢体缺血患者,应开发新的治疗策略,如再生疗法。间充质干细胞(MSCs)是再生疗法中最受欢迎的细胞来源。间充质干细胞具有血管生成、抗炎和免疫调节等重要特性,因此被广泛应用于不同疾病的治疗。这项 I 期临床试验报告了肌肉注射异体沃顿果冻间充质干细胞(WJ-MSCs)治疗 2 型糖尿病 CLI 患者的安全性、可行性和可能的疗效。在筛选出的六名慢性缺血性心肌梗死患者中,有五名患者在缺血下肢的腓肠肌、比目鱼肌和胫骨前肌近端注射了WJ-间充质干细胞。WJ-间充质干细胞注射的安全性被视为主要结果。次要终点包括伤口愈合、发病部位有无脉搏、有无截肢、视觉模拟量表(VAS)改善情况、无痛行走时间以及足踝残疾指数(FADI)。在 6 个月的随访中,没有患者出现不良反应和足部甚至脚趾截肢。干预6个月后,患者的VAS评分明显低于基线,无痛行走时间和FADI评分明显高于基线,但其他时间点之间的差异无统计学意义。总之,对CLI患者进行异体WJ-间充质干细胞移植似乎是安全有效的。
{"title":"Wharton’s jelly mesenchymal stem cells transplantation for critical limb ischemia in patients with type 2 diabetes mellitus: a preliminary report of phase I clinical trial","authors":"Mohammad Taghi Ashoobi, Hossein Hemmati, Hamid Reza Aghayan, Zeinab Zarei-Behjani, Samaneh Keshavarz, Hamideh Babaloo, Saman Maroufizadeh, Saeed Yousefi, Mohaya Farzin, Elham Vojoudi","doi":"10.1007/s00441-023-03854-7","DOIUrl":"https://doi.org/10.1007/s00441-023-03854-7","url":null,"abstract":"<p>Peripheral artery disease (PAD) affects more than 230 million people worldwide, with approximately 11% of patients presenting with advanced-stage PAD or critical limb ischemia (CLI). To avoid or delay amputation, particularly in no-option CLI patients with infeasible or ineffective revascularization, new treatment strategies such as regenerative therapies should be developed. Mesenchymal stem cells (MSCs) are the most popular cell source in regenerative therapies. They possess significant characteristics such as angiogenic, anti-inflammatory, and immunomodulatory activities, which encourage their application in different diseases. This phase I clinical trial reports the safety, feasibility, and probable efficacy of the intramuscular administration of allogeneic Wharton’s jelly-derived MSCs (WJ-MSCs) in type 2 diabetes patients with CLI. Out of six screened patients with CLI, five patients were administered WJ-MSCs into the gastrocnemius, soleus, and the proximal part of the tibialis anterior muscles of the ischemic lower limb. The safety of WJ-MSCs injection was considered a primary outcome. Secondary endpoints included wound healing, the presence of pulse at the disease site, the absence of amputation, and improvement in visual analogue scale (VAS), pain-free walking time, and foot and ankle disability index (FADI). No patient experienced adverse events and foot or even toe amputation during the 6-month follow-up. Six months after the intervention, there were a significantly lower VAS score and significantly higher pain-free walking time and FADI score than the baseline, but no statistically significant difference was seen between other time points. In conclusion, allogeneic WJ-MSC transplantation in patients with CLI seems to be safe and effective.</p>","PeriodicalId":9712,"journal":{"name":"Cell and Tissue Research","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2023-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138741705","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-15DOI: 10.1007/s00441-023-03853-8
E. R. Akhmetzyanova, A. A. Rizvanov, Y. O. Mukhamedshina
Microglia represent a distinct population of neuroglia, constituting ~ 10% of all CNS cells and exhibit high plasticity. Proper functioning of microglia is critical in the event of CNS damage due to the rapid modulation of their functions. Microglia are not only the first stage of immune defense against injury and infection, contributing to both the innate and adaptive local immune response, but also play a vital role in maintaining homeostasis of the brain and spinal cord. For this reason, microglia deserve special attention in the study of neuropathological responses. Studying microglia behavior in various in vivo models of neuropathologies is certainly a priority, as it allows us to evaluate the behavior in the context of the changing microenvironment of nervous tissue. However, sometimes there are some technological problems that hinder the identification of the features of intercellular interactions, ensured cooperation between microglia and other cell types. In this regard, the use of in vitro models remains relevant today, contributing to a more in-depth understanding of the mechanisms of microglial involvement in neuropathology. The methods considered in this review for obtaining an isolated culture of microglia, along with their advantages and disadvantages, can help researchers in selecting the appropriate source and method for obtaining these cells, thereby opening up opportunities for gaining new neurobiological knowledge.
{"title":"Current methods for the microglia isolation: Overview and comparative analysis of approaches","authors":"E. R. Akhmetzyanova, A. A. Rizvanov, Y. O. Mukhamedshina","doi":"10.1007/s00441-023-03853-8","DOIUrl":"https://doi.org/10.1007/s00441-023-03853-8","url":null,"abstract":"<p>Microglia represent a distinct population of neuroglia, constituting ~ 10% of all CNS cells and exhibit high plasticity. Proper functioning of microglia is critical in the event of CNS damage due to the rapid modulation of their functions. Microglia are not only the first stage of immune defense against injury and infection, contributing to both the innate and adaptive local immune response, but also play a vital role in maintaining homeostasis of the brain and spinal cord. For this reason, microglia deserve special attention in the study of neuropathological responses. Studying microglia behavior in various in vivo models of neuropathologies is certainly a priority, as it allows us to evaluate the behavior in the context of the changing microenvironment of nervous tissue. However, sometimes there are some technological problems that hinder the identification of the features of intercellular interactions, ensured cooperation between microglia and other cell types. In this regard, the use of in vitro models remains relevant today, contributing to a more in-depth understanding of the mechanisms of microglial involvement in neuropathology. The methods considered in this review for obtaining an isolated culture of microglia, along with their advantages and disadvantages, can help researchers in selecting the appropriate source and method for obtaining these cells, thereby opening up opportunities for gaining new neurobiological knowledge.</p>","PeriodicalId":9712,"journal":{"name":"Cell and Tissue Research","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2023-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138691121","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-13DOI: 10.1007/s00441-023-03852-9
Shashank Tripathi, Shweta Maurya, Ajit Singh
Adropin, a multifaceted peptide, was identified as a new metabolic hormone responsible for regulating gluco-lipid homeostasis. However, its role in the testicular function is not yet understood. We aimed to investigate the localization and expression of adropin and GPR19 during different phases of postnatal development. Immunohistochemical study revealed the intense reactivity of adropin in the Leydig cells during all phases of postnatal development, while GPR19 showed intense immunoreactivity in the pachytene spermatocytes and mild immunoreactivity in Leydig cells as well as primary and secondary spermatocytes. Western blot study revealed maximum expression of GPR19 in pre-pubertal mouse testis that clearly indicates maximum responsiveness of adropin during that period. So, we hypothesized that adropin may act as an autocrine/paracrine factor that regulates pubertal changes in mouse testis. To examine the effect of adropin on pubertal onset, we gave bilateral intra-testicular doses (0.5 and 1.5 µg/testis) to pre-pubertal mice. Adropin treatment promoted testicular testosterone synthesis by increasing the expression of StAR, 3β-HSD, and 17β-HSD. Adropin also promoted germ cell survival and proliferation by upregulating the expression of PCNA and downregulating the Bax/Bcl2 ratio and Caspase 3 expression resulting in fewer TUNEL-positive cells in adropin-treated groups. FACS analysis demonstrated that adropin treatment not only increases 1C to 4C ratio but also significantly increases the 1C (spermatid) and 1C to 2C ratio which demarcates accelerated germ cell differentiation and turnover of testicular cells. In conclusion, adropin promotes steroidogenesis, germ cell survival, as well as the proliferation in the pre-pubertal mouse testis that may hasten the pubertal transition in an autocrine/paracrine manner.
{"title":"Adropin, a novel hepatokine: localization and expression during postnatal development and its impact on testicular functions of pre-pubertal mice","authors":"Shashank Tripathi, Shweta Maurya, Ajit Singh","doi":"10.1007/s00441-023-03852-9","DOIUrl":"https://doi.org/10.1007/s00441-023-03852-9","url":null,"abstract":"<p>Adropin, a multifaceted peptide, was identified as a new metabolic hormone responsible for regulating gluco-lipid homeostasis. However, its role in the testicular function is not yet understood. We aimed to investigate the localization and expression of adropin and GPR19 during different phases of postnatal development. Immunohistochemical study revealed the intense reactivity of adropin in the Leydig cells during all phases of postnatal development, while GPR19 showed intense immunoreactivity in the pachytene spermatocytes and mild immunoreactivity in Leydig cells as well as primary and secondary spermatocytes. Western blot study revealed maximum expression of GPR19 in pre-pubertal mouse testis that clearly indicates maximum responsiveness of adropin during that period. So, we hypothesized that adropin may act as an autocrine/paracrine factor that regulates pubertal changes in mouse testis. To examine the effect of adropin on pubertal onset, we gave bilateral intra-testicular doses (0.5 and 1.5 µg/testis) to pre-pubertal mice. Adropin treatment promoted testicular testosterone synthesis by increasing the expression of StAR, 3β-HSD, and 17β-HSD. Adropin also promoted germ cell survival and proliferation by upregulating the expression of PCNA and downregulating the Bax/Bcl2 ratio and Caspase 3 expression resulting in fewer TUNEL-positive cells in adropin-treated groups. FACS analysis demonstrated that adropin treatment not only increases 1C to 4C ratio but also significantly increases the 1C (spermatid) and 1C to 2C ratio which demarcates accelerated germ cell differentiation and turnover of testicular cells. In conclusion, adropin promotes steroidogenesis, germ cell survival, as well as the proliferation in the pre-pubertal mouse testis that may hasten the pubertal transition in an autocrine/paracrine manner.</p>","PeriodicalId":9712,"journal":{"name":"Cell and Tissue Research","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2023-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138632542","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-13DOI: 10.1007/s00441-023-03850-x
H. M. Bjørgen, S. Malik, E. Rimstad, M. Vaadal, I. B. Nyman, E. O. Koppang, T. Tengs
Spatial transcriptomics is a technique that provides insight into gene expression profiles in tissue sections while retaining structural information. We have employed this method to study the pathological conditions related to red and melanized focal changes in farmed Atlantic salmon (Salmo salar). Our findings support a model where similar molecular mechanisms are involved in both red and melanized filet discolorations and genes associated with several relevant pathways show distinct expression patterns in both sample types. Interestingly, there appears to be significant cellular heterogeneity in the foci investigated when looking at gene expression patterns. Some of the genes that show differential spatial expression are involved in cellular processes such as hypoxia and immune responses, providing new insight into the nature of muscle melanization in Atlantic salmon.
{"title":"Cellular heterogeneity in red and melanized focal muscle changes in farmed Atlantic salmon (Salmo salar) visualized by spatial transcriptomics","authors":"H. M. Bjørgen, S. Malik, E. Rimstad, M. Vaadal, I. B. Nyman, E. O. Koppang, T. Tengs","doi":"10.1007/s00441-023-03850-x","DOIUrl":"https://doi.org/10.1007/s00441-023-03850-x","url":null,"abstract":"<p>Spatial transcriptomics is a technique that provides insight into gene expression profiles in tissue sections while retaining structural information. We have employed this method to study the pathological conditions related to red and melanized focal changes in farmed Atlantic salmon (<i>Salmo salar</i>). Our findings support a model where similar molecular mechanisms are involved in both red and melanized filet discolorations and genes associated with several relevant pathways show distinct expression patterns in both sample types. Interestingly, there appears to be significant cellular heterogeneity in the foci investigated when looking at gene expression patterns. Some of the genes that show differential spatial expression are involved in cellular processes such as hypoxia and immune responses, providing new insight into the nature of muscle melanization in Atlantic salmon. </p>","PeriodicalId":9712,"journal":{"name":"Cell and Tissue Research","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2023-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138632863","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bilateria share sequential steps in their digestive systems, and digestion occurs in a pre-absorption step within a chamber-like structure. Previous studies on the ascidian Ciona intestinalis type A, an evolutionary research model of vertebrate organs, revealed that Ciona homologs of pancreas-related exocrine digestive enzymes (XDEs) are exclusively expressed in the chamber-like bulging stomach. In the development of the gastrointestinal tract, genes for the pancreas-related transcription factors, namely Ptf1a, Nr5a2, and Pdx, are expressed near the stomach. Recent organ/tissue RNA-seq studies on two Ciona species reported that transcripts of the XDE homologs exist in the intestinal regions, as well as in the stomach. In the present study, we investigated the spatial gene expression of XDE homologs in the gastrointestinal region of the C. intestinalis type A. Whole-mount in situ hybridization using adult and juvenile specimens revealed apparent expression signals of XDE homologs in a small number of gastrointestinal epithelial cells. Furthermore, two pancreas-related transcription factor genes, Nr5a2 and Pdx, exhibited multi-regional expression along the Ciona juvenile intestines. These results imply that ascidians may form multiple digestive regions corresponding to the vertebrate pancreas.
{"title":"Multi-regional expression of pancreas-related digestive enzyme genes in the intestinal chamber of the ascidian Ciona intestinalis type A.","authors":"Rin Iguchi, Kanae Usui, Satoshi Nakayama, Yasunori Sasakura, Toshio Sekiguchi, Michio Ogasawara","doi":"10.1007/s00441-023-03839-6","DOIUrl":"10.1007/s00441-023-03839-6","url":null,"abstract":"<p><p>Bilateria share sequential steps in their digestive systems, and digestion occurs in a pre-absorption step within a chamber-like structure. Previous studies on the ascidian Ciona intestinalis type A, an evolutionary research model of vertebrate organs, revealed that Ciona homologs of pancreas-related exocrine digestive enzymes (XDEs) are exclusively expressed in the chamber-like bulging stomach. In the development of the gastrointestinal tract, genes for the pancreas-related transcription factors, namely Ptf1a, Nr5a2, and Pdx, are expressed near the stomach. Recent organ/tissue RNA-seq studies on two Ciona species reported that transcripts of the XDE homologs exist in the intestinal regions, as well as in the stomach. In the present study, we investigated the spatial gene expression of XDE homologs in the gastrointestinal region of the C. intestinalis type A. Whole-mount in situ hybridization using adult and juvenile specimens revealed apparent expression signals of XDE homologs in a small number of gastrointestinal epithelial cells. Furthermore, two pancreas-related transcription factor genes, Nr5a2 and Pdx, exhibited multi-regional expression along the Ciona juvenile intestines. These results imply that ascidians may form multiple digestive regions corresponding to the vertebrate pancreas.</p>","PeriodicalId":9712,"journal":{"name":"Cell and Tissue Research","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50157139","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-01Epub Date: 2023-10-31DOI: 10.1007/s00441-023-03838-7
Laura Steingruber, Florian Krabichler, Sophie Franzmeier, Wei Wu, Jürgen Schlegel, Marco Koch
ALDH1A1 and ALDH1A3 paralogues of aldehyde dehydrogenase 1 (ALDH1) control myogenic differentiation of skeletal muscle satellite cells (SC) by formation of retinoic acid (RA) and subsequent cell cycle adjustments. The respective relevance of each paralogue for myogenic differentiation and the mechanistic interaction of each paralogue within RA-dependent and RA-independent pathways remain elusive.We analysed the impact of ALDH1A1 and ALDH1A3 activity on myogenesis of murine C2C12 myoblasts. Both paralogues are pivotal factors in myogenic differentiation, since CRISPR/Cas9-edited single paralogue knock-out impaired serum withdrawal-induced myogenic differentiation, while successive recombinant re-expression of ALDH1A1 or ALDH1A3, respectively, in the corresponding ALDH1 paralogue single knock-out cell lines, recovered the differentiation potential. Loss of differentiation in single knock-out cell lines was restored by treatment with RA-analogue TTNPB, while RA-receptor antagonization by AGN 193109 inhibited differentiation of wildtype cell lines, supporting the idea that RA-dependent pathway is pivotal for myogenic differentiation which is accomplished by both paralogues.However, overexpression of ALDH1-paralogues or disulfiram-mediated inhibition of ALDH1 enzymatic activity not only increased ALDH1A1 and ALDH1A3 protein levels but also induced subsequent differentiation of C2C12 myoblasts independently from serum withdrawal, indicating that ALDH1-dependent myogenic differentiation relies on different cellular conditions. Remarkably, ALDH1-paralogue knock-out impaired the autophagic flux, namely autophagosome cargo protein p62 formation and LC3B-I to LC3B-II conversion, demonstrating that ALDH1-paralogues interact with autophagy in myogenesis. Together, ALDH1 paralogues play a crucial role in myogenesis by orchestration of complex RA-dependent and RA-independent pathways.
{"title":"ALDH1A1 and ALDH1A3 paralogues of aldehyde dehydrogenase 1 control myogenic differentiation of skeletal muscle satellite cells by retinoic acid-dependent and -independent mechanisms.","authors":"Laura Steingruber, Florian Krabichler, Sophie Franzmeier, Wei Wu, Jürgen Schlegel, Marco Koch","doi":"10.1007/s00441-023-03838-7","DOIUrl":"10.1007/s00441-023-03838-7","url":null,"abstract":"<p><p>ALDH1A1 and ALDH1A3 paralogues of aldehyde dehydrogenase 1 (ALDH1) control myogenic differentiation of skeletal muscle satellite cells (SC) by formation of retinoic acid (RA) and subsequent cell cycle adjustments. The respective relevance of each paralogue for myogenic differentiation and the mechanistic interaction of each paralogue within RA-dependent and RA-independent pathways remain elusive.We analysed the impact of ALDH1A1 and ALDH1A3 activity on myogenesis of murine C2C12 myoblasts. Both paralogues are pivotal factors in myogenic differentiation, since CRISPR/Cas9-edited single paralogue knock-out impaired serum withdrawal-induced myogenic differentiation, while successive recombinant re-expression of ALDH1A1 or ALDH1A3, respectively, in the corresponding ALDH1 paralogue single knock-out cell lines, recovered the differentiation potential. Loss of differentiation in single knock-out cell lines was restored by treatment with RA-analogue TTNPB, while RA-receptor antagonization by AGN 193109 inhibited differentiation of wildtype cell lines, supporting the idea that RA-dependent pathway is pivotal for myogenic differentiation which is accomplished by both paralogues.However, overexpression of ALDH1-paralogues or disulfiram-mediated inhibition of ALDH1 enzymatic activity not only increased ALDH1A1 and ALDH1A3 protein levels but also induced subsequent differentiation of C2C12 myoblasts independently from serum withdrawal, indicating that ALDH1-dependent myogenic differentiation relies on different cellular conditions. Remarkably, ALDH1-paralogue knock-out impaired the autophagic flux, namely autophagosome cargo protein p62 formation and LC3B-I to LC3B-II conversion, demonstrating that ALDH1-paralogues interact with autophagy in myogenesis. Together, ALDH1 paralogues play a crucial role in myogenesis by orchestration of complex RA-dependent and RA-independent pathways.</p>","PeriodicalId":9712,"journal":{"name":"Cell and Tissue Research","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71410901","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-01Epub Date: 2023-08-31DOI: 10.1007/s00441-023-03829-8
Yukio Kato, Saishu Yoshida, Takako Kato
The pituitary gland is a major endocrine tissue composing of two distinct entities, the adenohypophysis (anterior pituitary, cranial placode origin) and the neurohypophysis (posterior pituitary, neural ectoderm origin), and plays important roles in maintaining vital homeostasis. This tissue is maintained by a slow, consistent cell-renewal system of adult stem/progenitor cells. Recent accumulating evidence shows that neural crest-, head mesenchyme-, and endoderm lineage cells invade during pituitary development and contribute to the maintenance of the adult pituitary gland. Based on these novel observations, this article discusses whether these lineage cells are involved in pituitary organogenesis, maintenance, regeneration, dysplasia, or tumors.
{"title":"Missing pieces of the pituitary puzzle: participation of extra-adenohypophyseal placode-lineage cells in the adult pituitary gland.","authors":"Yukio Kato, Saishu Yoshida, Takako Kato","doi":"10.1007/s00441-023-03829-8","DOIUrl":"10.1007/s00441-023-03829-8","url":null,"abstract":"<p><p>The pituitary gland is a major endocrine tissue composing of two distinct entities, the adenohypophysis (anterior pituitary, cranial placode origin) and the neurohypophysis (posterior pituitary, neural ectoderm origin), and plays important roles in maintaining vital homeostasis. This tissue is maintained by a slow, consistent cell-renewal system of adult stem/progenitor cells. Recent accumulating evidence shows that neural crest-, head mesenchyme-, and endoderm lineage cells invade during pituitary development and contribute to the maintenance of the adult pituitary gland. Based on these novel observations, this article discusses whether these lineage cells are involved in pituitary organogenesis, maintenance, regeneration, dysplasia, or tumors.</p>","PeriodicalId":9712,"journal":{"name":"Cell and Tissue Research","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10178023","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-01Epub Date: 2023-10-18DOI: 10.1007/s00441-023-03834-x
Shouzhang Yang, Xiaojiao Ruan, Bingren Hu, Jinfu Tu, Huajie Cai
Liver cancer stem cell (CSC) self-renewal and tumorigenesis are important causes of hepatocellular carcinoma (HCC) recurrence. We purposed to investigate the function of long noncoding RNA small nucleolar RNA host gene 9 (SNHG9) in liver CSC self-renewal and tumorigenesis in this study. Flow cytometry was carried out to separate CD133+ Populations and CD133- Populations from HCC cell lines. A combination of CD133+ cells and Matrigel matrix was subcutaneously injected to create the NOD-SCID mouse xenograft tumor model. Colony formation test and spheroids formation assay were carried out to clarify the impact of SNHG9 on the self-renewal of liver CSCs. RNA immunoprecipitation, RNA-pull down, and chromatin immunoprecipitation were performed on CD133+ cells to elucidate the mechanism of SNHG9 regulating PTEN expression. We found that SNHG9 was highly expressed in HCC clinical samples, HCC cells, and CD133+ cells. In vitro, interference with SNHG9 prevented the formation of colonies and spheroids in liver CSC cells and primary HCC cells. In vivo, interference with SNHG9 reduced the tumor volume and weight. SNHG9 could bind to EZH2, and SNHG9 interference suppressed EZH2 recruitment and H3K27me3 levels in the PTEN promoter region. In addition, SNHG9 inhibition promoted PTEN expression while having little impact on EZH2 levels. Interference with SNHG9 inhibited liver CSC self-renewal and tumorigenesis by up-regulating PTEN levels. In conclusion, by binding to EZH2, SNHG9 down-regulated PTEN levels, promoting liver CSC self-renewal and tumor formation, and exacerbating HCC progression.
{"title":"lncRNA SNHG9 enhances liver cancer stem cell self-renewal and tumorigenicity by negatively regulating PTEN expression via recruiting EZH2.","authors":"Shouzhang Yang, Xiaojiao Ruan, Bingren Hu, Jinfu Tu, Huajie Cai","doi":"10.1007/s00441-023-03834-x","DOIUrl":"10.1007/s00441-023-03834-x","url":null,"abstract":"<p><p>Liver cancer stem cell (CSC) self-renewal and tumorigenesis are important causes of hepatocellular carcinoma (HCC) recurrence. We purposed to investigate the function of long noncoding RNA small nucleolar RNA host gene 9 (SNHG9) in liver CSC self-renewal and tumorigenesis in this study. Flow cytometry was carried out to separate CD133<sup>+</sup> Populations and CD133<sup>-</sup> Populations from HCC cell lines. A combination of CD133<sup>+</sup> cells and Matrigel matrix was subcutaneously injected to create the NOD-SCID mouse xenograft tumor model. Colony formation test and spheroids formation assay were carried out to clarify the impact of SNHG9 on the self-renewal of liver CSCs. RNA immunoprecipitation, RNA-pull down, and chromatin immunoprecipitation were performed on CD133<sup>+</sup> cells to elucidate the mechanism of SNHG9 regulating PTEN expression. We found that SNHG9 was highly expressed in HCC clinical samples, HCC cells, and CD133<sup>+</sup> cells. In vitro, interference with SNHG9 prevented the formation of colonies and spheroids in liver CSC cells and primary HCC cells. In vivo, interference with SNHG9 reduced the tumor volume and weight. SNHG9 could bind to EZH2, and SNHG9 interference suppressed EZH2 recruitment and H3K27me3 levels in the PTEN promoter region. In addition, SNHG9 inhibition promoted PTEN expression while having little impact on EZH2 levels. Interference with SNHG9 inhibited liver CSC self-renewal and tumorigenesis by up-regulating PTEN levels. In conclusion, by binding to EZH2, SNHG9 down-regulated PTEN levels, promoting liver CSC self-renewal and tumor formation, and exacerbating HCC progression.</p>","PeriodicalId":9712,"journal":{"name":"Cell and Tissue Research","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41232622","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}