Soo Bin Jang, Yoojung Kim, Han Ceol Yeo, Geun-Ho Kang, Byung Chull An, Yongku Ryu, Myung-Jun Chung, Ssang-Goo Cho
Probiotics exert various effects on the body and provide different health benefits. Previous reports have demonstrated that the P8 protein (P8), isolated from Lactobacillus rhamnosus, has anticancer properties. However, its efficacy in stem cells and normal cells has not been reported. In this study, the effect of P8 on cell proliferation and wound healing was evaluated, investigating its underlying mechanism. Based on scratch assay results, we demonstrated that P8 treatment significantly increases wound healing by activating the cell cycle and promoting stem cell stemness. Cellular mechanisms were further investigated by culturing stem cells in a medium containing Lactobacillus-derived P8 protein, revealing its promotion of cell proliferation and migration. Also, it is found that P8 enhances the expression of stemness markers, such as OCT4 and SOX2, along with activation of the mitogen-activated protein kinase (MAPK) signaling and Hippo pathways. These results indicate that P8 can promote cell growth by increasing stem cell proliferation, migration, and stemness in a manner associated with MAPK and Hippo signaling, which could contribute to the increased wound healing after P8 treatment. Furthermore, P8 could promote wound healing in keratinocytes by activating the MAPK signaling pathways. These results suggest that P8 might be a promising candidate to enhance stem cell culture efficiency by activating cell proliferation, and enhance therapeutic effects in skin diseases.
{"title":"Probiotic-Derived P8 Protein: Promoting Proliferation and Migration in Stem Cells and Keratinocytes.","authors":"Soo Bin Jang, Yoojung Kim, Han Ceol Yeo, Geun-Ho Kang, Byung Chull An, Yongku Ryu, Myung-Jun Chung, Ssang-Goo Cho","doi":"10.15283/ijsc24107","DOIUrl":"https://doi.org/10.15283/ijsc24107","url":null,"abstract":"<p><p>Probiotics exert various effects on the body and provide different health benefits. Previous reports have demonstrated that the P8 protein (P8), isolated from <i>Lactobacillus rhamnosus</i>, has anticancer properties. However, its efficacy in stem cells and normal cells has not been reported. In this study, the effect of P8 on cell proliferation and wound healing was evaluated, investigating its underlying mechanism. Based on scratch assay results, we demonstrated that P8 treatment significantly increases wound healing by activating the cell cycle and promoting stem cell stemness. Cellular mechanisms were further investigated by culturing stem cells in a medium containing Lactobacillus-derived P8 protein, revealing its promotion of cell proliferation and migration. Also, it is found that P8 enhances the expression of stemness markers, such as <i>OCT4</i> and <i>SOX2</i>, along with activation of the mitogen-activated protein kinase (MAPK) signaling and Hippo pathways. These results indicate that P8 can promote cell growth by increasing stem cell proliferation, migration, and stemness in a manner associated with MAPK and Hippo signaling, which could contribute to the increased wound healing after P8 treatment. Furthermore, P8 could promote wound healing in keratinocytes by activating the MAPK signaling pathways. These results suggest that P8 might be a promising candidate to enhance stem cell culture efficiency by activating cell proliferation, and enhance therapeutic effects in skin diseases.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142568396","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Geun-Ho Kang, Yeo Kyung Shin, Kyung Min Lim, Se Jong Kim, Myeongjin Song, Kwonwoo Song, Jung Hyun Kim, Dae Young Kim, Hang-Cheol Shin, Hyun Jin Shin, Ssang-Goo Cho
Stem cells derived from human orbicularis oculi muscle (hOOM) are a valuable resource for cell therapy. However, when stem cells are continuously cultured, their abilities tend to deteriorate over time. One method to address this issue is to use basic fibroblast growth factor (bFGF) to maintain the stem cell functionality. The limitation is that bFGF is unstable under mammalian cell culture conditions with a half-life of only 8 hours, which poses a significant challenge to the production and maintenance of high-quality stem cells. In this study, we used thermostable bFGF (TS-bFGF) and demonstrated that hOOM-derived stem cells cultured with TS-bFGF exhibited superior proliferation, stem cell function, reduced reactive oxygen species, and cellular senescence delay effect compared to cells cultured with wild-type bFGF. Considering the pivotal role of stem cells in broad ranges of applications such as regenerative medicine and cultured meat, we anticipate that TS-bFGF, owing to its thermostability and long-lasting properties, will contribute significantly to the acquisition of high-quality stem cells.
{"title":"Thermostable bFGF Improves Cell Lifespan by Enhancing Cell Activity in the Long-Term Culture of Human Orbicularis Oculi Stem Cells.","authors":"Geun-Ho Kang, Yeo Kyung Shin, Kyung Min Lim, Se Jong Kim, Myeongjin Song, Kwonwoo Song, Jung Hyun Kim, Dae Young Kim, Hang-Cheol Shin, Hyun Jin Shin, Ssang-Goo Cho","doi":"10.15283/ijsc24039","DOIUrl":"https://doi.org/10.15283/ijsc24039","url":null,"abstract":"<p><p>Stem cells derived from human orbicularis oculi muscle (hOOM) are a valuable resource for cell therapy. However, when stem cells are continuously cultured, their abilities tend to deteriorate over time. One method to address this issue is to use basic fibroblast growth factor (bFGF) to maintain the stem cell functionality. The limitation is that bFGF is unstable under mammalian cell culture conditions with a half-life of only 8 hours, which poses a significant challenge to the production and maintenance of high-quality stem cells. In this study, we used thermostable bFGF (TS-bFGF) and demonstrated that hOOM-derived stem cells cultured with TS-bFGF exhibited superior proliferation, stem cell function, reduced reactive oxygen species, and cellular senescence delay effect compared to cells cultured with wild-type bFGF. Considering the pivotal role of stem cells in broad ranges of applications such as regenerative medicine and cultured meat, we anticipate that TS-bFGF, owing to its thermostability and long-lasting properties, will contribute significantly to the acquisition of high-quality stem cells.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142500566","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Dat Ngo, Jeongmin Lee, Sun Jae Kwon, Jin Hun Park, Baek Hwan Cho, Jong Wook Chang
Current image-based analysis methods for monitoring cell confluency and status depend on individual interpretations, which can lead to wide variations in the quality of cell therapeutics. To overcome these limitations, images of mesenchymal stem cells cultured adherently in various types of culture vessels were captured and analyzed using a deep neural network. Among the various deep learning methods, a classification and detection algorithm was selected to verify cell confluency and status. We confirmed that the image classification algorithm demonstrates significant accuracy for both single- and multistack images. Abnormal cells could be detected exclusively in single-stack images, as multistack culture was performed only when abnormal cells were absent in the single-stack culture. This study is the first to analyze cell images based on a deep learning method that directly impacts yield and quality, which are important product parameters in stem cell therapeutics.
{"title":"Application of Deep Neural Networks in the Manufacturing Process of Mesenchymal Stem Cells Therapeutics.","authors":"Dat Ngo, Jeongmin Lee, Sun Jae Kwon, Jin Hun Park, Baek Hwan Cho, Jong Wook Chang","doi":"10.15283/ijsc24070","DOIUrl":"https://doi.org/10.15283/ijsc24070","url":null,"abstract":"<p><p>Current image-based analysis methods for monitoring cell confluency and status depend on individual interpretations, which can lead to wide variations in the quality of cell therapeutics. To overcome these limitations, images of mesenchymal stem cells cultured adherently in various types of culture vessels were captured and analyzed using a deep neural network. Among the various deep learning methods, a classification and detection algorithm was selected to verify cell confluency and status. We confirmed that the image classification algorithm demonstrates significant accuracy for both single- and multistack images. Abnormal cells could be detected exclusively in single-stack images, as multistack culture was performed only when abnormal cells were absent in the single-stack culture. This study is the first to analyze cell images based on a deep learning method that directly impacts yield and quality, which are important product parameters in stem cell therapeutics.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142346749","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ki-Sang Jo,Won-Jun Jo,Ainsley Mike Antao,Janardhan Keshav Karapurkar,Young Jun Park,Myeong-Jun Choi,Suresh Ramakrishna,Kye-Seong Kim
Bioactive lipids like sphingosine-1-phosphate (S1P) and lysophosphatidic acid have gained significant attention as signaling molecules with regulatory roles in stem cell proliferation and differentiation. The novel chemically synthesized sphingosine metabolite O-cyclic phytosphingosine-1-phosphate (cP1P) is derived from phytosphingosine-1-phosphate (P1P) and shares structural similarities with S1P. Previously, the role of cP1P in regulating ALK3/BMPR signaling during cardiomyocyte differentiation from human embryonic stem cells (hESCs) was demonstrated. In this study, the applicability of cP1P for endothelial cells (ECs) differentiation from hESCs was investigated an efficient method to obtain a high yield of functional ECs over several passages was standardized. The ECs derived from hESCs showed cellular and molecular characteristics similar to the native ECs. Thus, the results of this study open avenues for further research into cP1P-based stem cell differentiation for regenerative therapies.
{"title":"An Efficient Endothelial Cell Differentiation Protocol Using Bioactive Lipid O-Cyclic Phytosphingosine-1-Phosphate in Human Embryonic Stem Cells.","authors":"Ki-Sang Jo,Won-Jun Jo,Ainsley Mike Antao,Janardhan Keshav Karapurkar,Young Jun Park,Myeong-Jun Choi,Suresh Ramakrishna,Kye-Seong Kim","doi":"10.15283/ijsc24068","DOIUrl":"https://doi.org/10.15283/ijsc24068","url":null,"abstract":"Bioactive lipids like sphingosine-1-phosphate (S1P) and lysophosphatidic acid have gained significant attention as signaling molecules with regulatory roles in stem cell proliferation and differentiation. The novel chemically synthesized sphingosine metabolite O-cyclic phytosphingosine-1-phosphate (cP1P) is derived from phytosphingosine-1-phosphate (P1P) and shares structural similarities with S1P. Previously, the role of cP1P in regulating ALK3/BMPR signaling during cardiomyocyte differentiation from human embryonic stem cells (hESCs) was demonstrated. In this study, the applicability of cP1P for endothelial cells (ECs) differentiation from hESCs was investigated an efficient method to obtain a high yield of functional ECs over several passages was standardized. The ECs derived from hESCs showed cellular and molecular characteristics similar to the native ECs. Thus, the results of this study open avenues for further research into cP1P-based stem cell differentiation for regenerative therapies.","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":"23 1","pages":""},"PeriodicalIF":2.3,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142187043","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Despite enormous efforts, no effective medication has been found to significantly halt or even slow the progression of neurological diseases, such as acquired (e.g., traumatic brain injury, spinal cord injury, etc.) and chronic (e.g., Parkinson's disease, Alzheimer's disease, etc.) central nervous system disorders. So, researchers are looking for alternative therapeutic modalities to manage the disease's symptoms and stop it from worsening. Concerning disease-modifying capabilities, stem cell therapy has emerged as an expanding domain. Among different types of stem cells, human endometrial regenerative cells have excellent regenerative properties, making them suitable for regenerative medicine. They have the potential for self-renewal and differentiation into three types of stem cells: epithelial stem cells, endothelial side population stem cells, and mesenchymal stem cells (MSCs). ERCs can be isolated from endometrial biopsy and menstrual blood samples. However, there is no comprehensive evidence on the effects of ERCs on neurological disorders. Hence, we initially explore the traits of these specific stem cells in this analysis, followed by an emphasis on their therapeutic potential in treating neurological disorders.
{"title":"Human Endometrial Regenerative Cells for Neurological Disorders: Hype or Hope?","authors":"Javad Momeni, Elnaz Naserzadeh, Ali Sepehrinezhad, Rezan Ashayeri Ahmadabad, Sajad Sahab Negah","doi":"10.15283/ijsc23091","DOIUrl":"10.15283/ijsc23091","url":null,"abstract":"<p><p>Despite enormous efforts, no effective medication has been found to significantly halt or even slow the progression of neurological diseases, such as acquired (e.g., traumatic brain injury, spinal cord injury, etc.) and chronic (e.g., Parkinson's disease, Alzheimer's disease, etc.) central nervous system disorders. So, researchers are looking for alternative therapeutic modalities to manage the disease's symptoms and stop it from worsening. Concerning disease-modifying capabilities, stem cell therapy has emerged as an expanding domain. Among different types of stem cells, human endometrial regenerative cells have excellent regenerative properties, making them suitable for regenerative medicine. They have the potential for self-renewal and differentiation into three types of stem cells: epithelial stem cells, endothelial side population stem cells, and mesenchymal stem cells (MSCs). ERCs can be isolated from endometrial biopsy and menstrual blood samples. However, there is no comprehensive evidence on the effects of ERCs on neurological disorders. Hence, we initially explore the traits of these specific stem cells in this analysis, followed by an emphasis on their therapeutic potential in treating neurological disorders.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":" ","pages":"224-235"},"PeriodicalIF":2.5,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11361851/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139377593","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Spinal cord injury (SCI) is a serious nervous system disease that usually leads to the impairment of the motor, sensory, and autonomic nervous functions of the spinal cord, and it places a heavy burden on families and healthcare systems every year. Due to the complex pathophysiological mechanism of SCI and the poor ability of neurons to regenerate, the current treatment scheme has very limited effects on the recovery of spinal cord function. In addition, due to their unique advantages, exosomes can be used as carriers for cargo transport. In recent years, some studies have confirmed that treatment with mesenchymal stem cells (MSCs) can promote the recovery of SCI nerve function. The therapeutic effect of MSCs is mainly related to exosomes secreted by MSCs, and exosomes may have great potential in SCI therapy. In this review, we summarized the repair mechanism of mesenchymal stem cells-derived exosomes (MSCs-Exos) in SCI treatment and discussed the microRNAs related to SCI treatment based on MSCs-Exos and their mechanism of action, which is helpful to further understand the role of exosomes in SCI.
{"title":"The Role of Exosomes from Mesenchymal Stem Cells in Spinal Cord Injury: A Systematic Review.","authors":"Haoyu Wang, Chunxia Zhao, Qingqing Rong, Jinghe Cao, Hongyi Chen, Ruolin Li, Bin Zhang, Peng Xu","doi":"10.15283/ijsc23092","DOIUrl":"10.15283/ijsc23092","url":null,"abstract":"<p><p>Spinal cord injury (SCI) is a serious nervous system disease that usually leads to the impairment of the motor, sensory, and autonomic nervous functions of the spinal cord, and it places a heavy burden on families and healthcare systems every year. Due to the complex pathophysiological mechanism of SCI and the poor ability of neurons to regenerate, the current treatment scheme has very limited effects on the recovery of spinal cord function. In addition, due to their unique advantages, exosomes can be used as carriers for cargo transport. In recent years, some studies have confirmed that treatment with mesenchymal stem cells (MSCs) can promote the recovery of SCI nerve function. The therapeutic effect of MSCs is mainly related to exosomes secreted by MSCs, and exosomes may have great potential in SCI therapy. In this review, we summarized the repair mechanism of mesenchymal stem cells-derived exosomes (MSCs-Exos) in SCI treatment and discussed the microRNAs related to SCI treatment based on MSCs-Exos and their mechanism of action, which is helpful to further understand the role of exosomes in SCI.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":" ","pages":"236-252"},"PeriodicalIF":2.5,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11361850/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138451460","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-30Epub Date: 2024-06-26DOI: 10.15283/ijsc24060
Youngjun Park, Eui Man Jeong
Glutathione (GSH), the main cellular antioxidant, dynamically influences tumor growth, metastasis, and resistance to therapy in the tumor microenvironment (TME), which comprises cancer cells, immune cells, stromal cells, and non-cellular components, including the extracellular matrix, metabolites, hypoxia, and acidity. Cancer stem cells (CSCs) and T cells are minor but significant cell subsets of the TME. GSH dynamics influences the fate of CSCs and T cells. Here, we explored GSH dynamics in CSCs and T cells within the TME, as well as therapeutic approaches that could target these dynamics.
{"title":"Glutathione Dynamics in the Tumor Microenvironment: A Potential Target of Cancer Stem Cells and T Cells.","authors":"Youngjun Park, Eui Man Jeong","doi":"10.15283/ijsc24060","DOIUrl":"10.15283/ijsc24060","url":null,"abstract":"<p><p>Glutathione (GSH), the main cellular antioxidant, dynamically influences tumor growth, metastasis, and resistance to therapy in the tumor microenvironment (TME), which comprises cancer cells, immune cells, stromal cells, and non-cellular components, including the extracellular matrix, metabolites, hypoxia, and acidity. Cancer stem cells (CSCs) and T cells are minor but significant cell subsets of the TME. GSH dynamics influences the fate of CSCs and T cells. Here, we explored GSH dynamics in CSCs and T cells within the TME, as well as therapeutic approaches that could target these dynamics.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":" ","pages":"270-283"},"PeriodicalIF":2.5,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11361844/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141450490","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-30Epub Date: 2024-07-12DOI: 10.15283/ijsc23105
Eun Jin Seo, Soyoung Park, Eungyung Lee, Yang Hoon Huh, Ye Eun Ha, Gabor J Tigyi, Taesung Jeong, Il Ho Jang, Jonghyun Shin
Mesenchymal stem cells in the dental tissue indicate a disposition for differentiation into diverse dental lineages and contain enormous potential as the important means for regenerative medicine in dentistry. Among various dental tissues, the dental pulp contains stem cells, progenitor cells and odontoblasts for maintaining dentin homeostasis. The conventional culture of stem cells holds a limit as the living tissue constitutes the three-dimensional (3D) structure. Recent development in the organoid cultures have successfully recapitulated 3D structure and advanced to the assembling of different types. In the current study, the protocol for 3D explant culture of the human dental pulp tissue has been established by adopting the organoid culture. After isolating dental pulp from human tooth, the intact tissue was placed between two layers for Matrigel with addition of the culture medium. The reticular outgrowth of pre-odontoblast layer continued for a month and the random accumulation of dentin was observed near the end. Electron microscopy showed the cellular organization and in situ development of dentin, and immunohistochemistry exhibited the expression of odontoblast and stem cell markers in the outgrowth area. Three-dimensional explant culture of human dental pulp will provide a novel platform for understanding stem cell biology inside the tooth and developing the regenerative medicine.
{"title":"Establishing Three-Dimensional Explant Culture of Human Dental Pulp Tissue.","authors":"Eun Jin Seo, Soyoung Park, Eungyung Lee, Yang Hoon Huh, Ye Eun Ha, Gabor J Tigyi, Taesung Jeong, Il Ho Jang, Jonghyun Shin","doi":"10.15283/ijsc23105","DOIUrl":"10.15283/ijsc23105","url":null,"abstract":"<p><p>Mesenchymal stem cells in the dental tissue indicate a disposition for differentiation into diverse dental lineages and contain enormous potential as the important means for regenerative medicine in dentistry. Among various dental tissues, the dental pulp contains stem cells, progenitor cells and odontoblasts for maintaining dentin homeostasis. The conventional culture of stem cells holds a limit as the living tissue constitutes the three-dimensional (3D) structure. Recent development in the organoid cultures have successfully recapitulated 3D structure and advanced to the assembling of different types. In the current study, the protocol for 3D explant culture of the human dental pulp tissue has been established by adopting the organoid culture. After isolating dental pulp from human tooth, the intact tissue was placed between two layers for Matrigel with addition of the culture medium. The reticular outgrowth of pre-odontoblast layer continued for a month and the random accumulation of dentin was observed near the end. Electron microscopy showed the cellular organization and <i>in situ</i> development of dentin, and immunohistochemistry exhibited the expression of odontoblast and stem cell markers in the outgrowth area. Three-dimensional explant culture of human dental pulp will provide a novel platform for understanding stem cell biology inside the tooth and developing the regenerative medicine.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":" ","pages":"330-336"},"PeriodicalIF":2.5,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11361853/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141590332","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-30Epub Date: 2024-01-16DOI: 10.15283/ijsc23093
Mingming Qin, Linzi Ma, Wenjing Du, Dingyao Chen, Guoqun Luo, Zhaoting Liu
Sine oculis homeobox 1 (Six1) is an important factor for embryonic development and carcinoma malignancy. However, the localization of Six1 varies due to protein size and cell types in different organs. In this study, we focus on the expression and localization of Six1 in male reproductive organ via bioinformatics analysis and immunofluorescent detection. The potential interacted proteins with Six1 were also predicted by protein-protein interactions (PPIs) and Enrichr analysis. Bioinformatic data from The Cancer Genome Atlas and Genotype-Tissue Expression project databases showed that SIX1 was highly expressed in normal human testis, but low expressed in the testicular germ cell tumor sample. Human Protein Atlas examination verified that SIX1 level was higher in normal than that in cancer samples. The sub-localization of SIX1 in different reproductive tissues varies but specifically in the cytoplasm and membrane in testicular cells. In mouse cells, single cell RNA-sequencing data analysis indicated that Six1 expression level was higher in mouse spermatogonial stem cells (mSSCs) and differentiating spermatogonial than in other somatic cells. Immunofluorescence staining showed the cytoplasmic localization of Six1 in mouse testis and mSSCs. Further PPIs and Enrichr examination showed the potential interaction of Six1 with bone morphogenetic protein 4 (Bmp4) and catenin Beta-1 (CtnnB1) and stem cell signal pathways. Cytoplasmic localization of Six1 in male testis and mSSCs was probably associated with stem cell related proteins Bmp4 and CtnnB1 for stem cell development.
Sine oculis homeobox 1(Six1)是胚胎发育和癌症恶变的重要因素。然而,由于蛋白质大小和细胞类型的不同,Six1 在不同器官中的定位也不尽相同。本研究通过生物信息学分析和免疫荧光检测,重点研究了Six1在男性生殖器官中的表达和定位。我们还通过蛋白-蛋白相互作用(PPIs)和Enrichr分析预测了与Six1潜在相互作用的蛋白。来自癌症基因组图谱和基因型-组织表达项目数据库的生物信息学数据显示,SIX1在正常人睾丸中高表达,但在睾丸生殖细胞肿瘤样本中低表达。人类蛋白质图谱(Human Protein Atlas)检查证实,正常样本中的 SIX1 水平高于癌症样本。SIX1 在不同生殖组织中的亚定位存在差异,但在睾丸细胞中特别定位于细胞质和细胞膜。在小鼠细胞中,单细胞 RNA 序列数据分析表明,小鼠精原干细胞(mSSCs)和分化精原细胞中的 Six1 表达水平高于其他体细胞。免疫荧光染色显示,在小鼠睾丸和mSSCs中,Six1定位于细胞质。进一步的PPIs和Enrichr检查显示,Six1可能与骨形态发生蛋白4(Bmp4)和Catenin Beta-1(CtnnB1)以及干细胞信号通路相互作用。Six1在雄性睾丸和mSSCs中的细胞质定位可能与干细胞相关蛋白Bmp4和CtnnB1有关,有助于干细胞发育。
{"title":"Cytoplasmatic Localization of Six1 in Male Testis and Spermatogonial Stem Cells.","authors":"Mingming Qin, Linzi Ma, Wenjing Du, Dingyao Chen, Guoqun Luo, Zhaoting Liu","doi":"10.15283/ijsc23093","DOIUrl":"10.15283/ijsc23093","url":null,"abstract":"<p><p>Sine oculis homeobox 1 (Six1) is an important factor for embryonic development and carcinoma malignancy. However, the localization of Six1 varies due to protein size and cell types in different organs. In this study, we focus on the expression and localization of Six1 in male reproductive organ via bioinformatics analysis and immunofluorescent detection. The potential interacted proteins with Six1 were also predicted by protein-protein interactions (PPIs) and Enrichr analysis. Bioinformatic data from The Cancer Genome Atlas and Genotype-Tissue Expression project databases showed that <i>SIX1</i> was highly expressed in normal human testis, but low expressed in the testicular germ cell tumor sample. Human Protein Atlas examination verified that SIX1 level was higher in normal than that in cancer samples. The sub-localization of SIX1 in different reproductive tissues varies but specifically in the cytoplasm and membrane in testicular cells. In mouse cells, single cell RNA-sequencing data analysis indicated that <i>Six1</i> expression level was higher in mouse spermatogonial stem cells (mSSCs) and differentiating spermatogonial than in other somatic cells. Immunofluorescence staining showed the cytoplasmic localization of Six1 in mouse testis and mSSCs. Further PPIs and Enrichr examination showed the potential interaction of Six1 with bone morphogenetic protein 4 (Bmp4) and catenin Beta-1 (CtnnB1) and stem cell signal pathways. Cytoplasmic localization of Six1 in male testis and mSSCs was probably associated with stem cell related proteins Bmp4 and CtnnB1 for stem cell development.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":" ","pages":"298-308"},"PeriodicalIF":2.5,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11361848/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139471942","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}