Pub Date : 2025-01-01DOI: 10.1016/j.diff.2024.100830
Bo Li , Shuang Zhang , Xiaoxian Yun , Chengyi Liu , Rui Xiao , Mingjie Lu , Xiaomei Xu , Fuwei Lin
Neural precursor cell expressed developmentally down-regulated 4 (NEDD4) is an E3 ubiquitin ligase implicated in craniofacial development. Emerging evidence suggests that NEDD4 may down-regulates Akt signaling, a key element of the PI3K/Akt pathway involved in cell differentiation. This study aimed to investigate NEDD4's role in bone mesenchymal stem cells (BMSCs) differentiation and its interaction with the PI3K/Akt pathway.
BMSCs were isolated from SD rats, and NEDD4 expression increased during osteogenic differentiation. Silencing NEDD4 with siRNA elevated alkaline phosphatase (ALP), osteocalcin (OCN), Akt, and mTORC1 expression during induction, while subsequent treatment with LY294002 (a broad spectrum PI3K inhibitor) reduced Akt, mTORC1, ALP, and OCN levels.
These findings suggest that NEDD4 may inhibit BMSCs differentiation by suppressing the PI3K/Akt pathway during osteogenesis.
{"title":"NEDD4's effect on osteoblastogenesis potential of bone mesenchymal stem cells in rats concerned with PI3K/Akt pathway","authors":"Bo Li , Shuang Zhang , Xiaoxian Yun , Chengyi Liu , Rui Xiao , Mingjie Lu , Xiaomei Xu , Fuwei Lin","doi":"10.1016/j.diff.2024.100830","DOIUrl":"10.1016/j.diff.2024.100830","url":null,"abstract":"<div><div>Neural precursor cell expressed developmentally down-regulated 4 (NEDD4) is an E3 ubiquitin ligase implicated in craniofacial development. Emerging evidence suggests that NEDD4 may down-regulates Akt signaling, a key element of the PI3K/Akt pathway involved in cell differentiation. This study aimed to investigate NEDD4's role in bone mesenchymal stem cells (BMSCs) differentiation and its interaction with the PI3K/Akt pathway.</div><div>BMSCs were isolated from SD rats, and NEDD4 expression increased during osteogenic differentiation. Silencing NEDD4 with siRNA elevated alkaline phosphatase (ALP), osteocalcin (OCN), Akt, and mTORC1 expression during induction, while subsequent treatment with LY294002 (a broad spectrum PI3K inhibitor) reduced Akt, mTORC1, ALP, and OCN levels.</div><div>These findings suggest that NEDD4 may inhibit BMSCs differentiation by suppressing the PI3K/Akt pathway during osteogenesis.</div></div>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":"141 ","pages":"Article 100830"},"PeriodicalIF":2.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142824782","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-01DOI: 10.1016/j.diff.2024.100832
Feiyi Duan , Jiaoyan Wu , Jiayi Chang , Haoyuan Peng , Zitao Liu , Pengfei Liu , Xu Han , Tiantian Sun , Dandan Shang , Yutian Yang , Zhihao Li , Pengkun Li , Yixuan Liu , Yonghao Zhu , Yunzhi Lv , Xiumei Guo , Ying Zhao , Yang An
Current research has found that adipose tissue is not only involved in energy metabolism, but also a highly active endocrine organ that secretes various adipokines, including adiponectin, leptin, resistin and apelin, which are involved in the regulation of physiology and pathology of tissues and organs throughout the body. With the yearly increasing incidence, obesity has become a risk factor for a variety of pathological changes, including inflammation and metabolic syndrome in various system (endocrine, circulatory, locomotor and central nervous system). Thus these symptoms lead to multi-organ dysfunctions, including the heart, liver, kidneys, brain and joints. An in-depth summary of the roles of adipokines in the regulation of other tissues and organs can help to provide more effective therapeutic strategies for obesity-related diseases and explore potential therapeutic targets. Therefore, this review has retrospected the endocrine function of adipose tissue under obesity and the role of dysregulated adipokine secretion in related diseases and the underlying mechanisms, in order to provide a theoretical basis for targeting adipokine-mediated systemic dysregulation.
{"title":"Deciphering endocrine function of adipose tissue and its significant influences in obesity-related diseases caused by its dysfunction","authors":"Feiyi Duan , Jiaoyan Wu , Jiayi Chang , Haoyuan Peng , Zitao Liu , Pengfei Liu , Xu Han , Tiantian Sun , Dandan Shang , Yutian Yang , Zhihao Li , Pengkun Li , Yixuan Liu , Yonghao Zhu , Yunzhi Lv , Xiumei Guo , Ying Zhao , Yang An","doi":"10.1016/j.diff.2024.100832","DOIUrl":"10.1016/j.diff.2024.100832","url":null,"abstract":"<div><div>Current research has found that adipose tissue is not only involved in energy metabolism, but also a highly active endocrine organ that secretes various adipokines, including adiponectin, leptin, resistin and apelin, which are involved in the regulation of physiology and pathology of tissues and organs throughout the body. With the yearly increasing incidence, obesity has become a risk factor for a variety of pathological changes, including inflammation and metabolic syndrome in various system (endocrine, circulatory, locomotor and central nervous system). Thus these symptoms lead to multi-organ dysfunctions, including the heart, liver, kidneys, brain and joints. An in-depth summary of the roles of adipokines in the regulation of other tissues and organs can help to provide more effective therapeutic strategies for obesity-related diseases and explore potential therapeutic targets. Therefore, this review has retrospected the endocrine function of adipose tissue under obesity and the role of dysregulated adipokine secretion in related diseases and the underlying mechanisms, in order to provide a theoretical basis for targeting adipokine-mediated systemic dysregulation.</div></div>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":"141 ","pages":"Article 100832"},"PeriodicalIF":2.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142878121","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 : 2025-01-01DOI: 10.1016/j.diff.2025.100834
Alexandra A. Vetrova , Stanislav V. Kremnyov
Most hydrozoan cnidarians form complex colonies that vary in size, shape, and branching patterns. However, little is known about the molecular genetic mechanisms responsible for the diversity of the hydrozoan body plans. The Nodal signaling pathway has previously been shown to be essential for setting up a new body axis in a budding Hydra. This budding process is often compared to the branching of colonial hydrozoans, suggesting that the signaling mechanisms underlying branching and budding are evolutionarily conserved. Using the colonial hydrozoan Dynamena pumila, we demonstrated that colony architecture depends on the activity level of SMAD2/3-mediated signaling. Pharmacological inhibition of the SMAD2/3-mediated Nodal signaling pathway resulted in an altered architecture of D. pumila primary colony, resembling naturally occurring malformation. Additionally, we identified a Nodal-related gene in D. pumila and observed its expression at the earliest stage of new colony module formation. Taken together, our results suggest that TGF-β signaling pathway plays an important role in shaping the morphology of hydrozoan colony.
{"title":"SMAD2/3 signaling determines the colony architecture in a hydrozoan, Dynamena pumila","authors":"Alexandra A. Vetrova , Stanislav V. Kremnyov","doi":"10.1016/j.diff.2025.100834","DOIUrl":"10.1016/j.diff.2025.100834","url":null,"abstract":"<div><div>Most hydrozoan cnidarians form complex colonies that vary in size, shape, and branching patterns. However, little is known about the molecular genetic mechanisms responsible for the diversity of the hydrozoan body plans. The Nodal signaling pathway has previously been shown to be essential for setting up a new body axis in a budding <em>Hydra</em>. This budding process is often compared to the branching of colonial hydrozoans, suggesting that the signaling mechanisms underlying branching and budding are evolutionarily conserved. Using the colonial hydrozoan <em>Dynamena pumila,</em> we demonstrated that colony architecture depends on the activity level of SMAD2/3-mediated signaling. Pharmacological inhibition of the SMAD2/3-mediated Nodal signaling pathway resulted in an altered architecture of <em>D. pumila</em> primary colony, resembling naturally occurring malformation. Additionally, we identified a <em>Nodal-related</em> gene in <em>D. pumila</em> and observed its expression at the earliest stage of new colony module formation. Taken together, our results suggest that TGF-β signaling pathway plays an important role in shaping the morphology of hydrozoan colony.</div></div>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":"141 ","pages":"Article 100834"},"PeriodicalIF":2.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143015525","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 : 2024-11-01DOI: 10.1016/j.diff.2024.100819
Samantha Bromley-Coolidge, Diego Iruegas, Bruce Appel
The extracellular matrix (ECM) provides critical biochemical and structural cues that regulate neural development. Chondroitin sulfate proteoglycans (CSPGs), a major ECM component, have been implicated in modulating oligodendrocyte precursor cell (OPC) proliferation, migration, and maturation, but their specific roles in oligodendrocyte lineage cell (OLC) development and myelination in vivo remain poorly understood. Here, we use zebrafish as a model system to investigate the spatiotemporal dynamics of ECM deposition and CSPG localization during central nervous system (CNS) development, with a focus on their relationship to OLCs. We demonstrate that ECM components, including CSPGs, are dynamically expressed in distinct spatiotemporal patterns coinciding with OLC development and myelination. We found that zebrafish lacking cspg4 function produced normal numbers of OLCs, which appeared to undergo proper differentiation. However, OPC morphology in mutant larvae was aberrant. Nevertheless, the number and length of myelin sheaths produced by mature oligodendrocytes were unaffected. These data indicate that Cspg4 regulates OPC morphogenesis in vivo, supporting the role of the ECM in neural development.
{"title":"Cspg4 sculpts oligodendrocyte precursor cell morphology","authors":"Samantha Bromley-Coolidge, Diego Iruegas, Bruce Appel","doi":"10.1016/j.diff.2024.100819","DOIUrl":"10.1016/j.diff.2024.100819","url":null,"abstract":"<div><div>The extracellular matrix (ECM) provides critical biochemical and structural cues that regulate neural development. Chondroitin sulfate proteoglycans (CSPGs), a major ECM component, have been implicated in modulating oligodendrocyte precursor cell (OPC) proliferation, migration, and maturation, but their specific roles in oligodendrocyte lineage cell (OLC) development and myelination <em>in vivo</em> remain poorly understood. Here, we use zebrafish as a model system to investigate the spatiotemporal dynamics of ECM deposition and CSPG localization during central nervous system (CNS) development, with a focus on their relationship to OLCs. We demonstrate that ECM components, including CSPGs, are dynamically expressed in distinct spatiotemporal patterns coinciding with OLC development and myelination. We found that zebrafish lacking <em>cspg4</em> function produced normal numbers of OLCs, which appeared to undergo proper differentiation. However, OPC morphology in mutant larvae was aberrant. Nevertheless, the number and length of myelin sheaths produced by mature oligodendrocytes were unaffected. These data indicate that <em>Cspg4</em> regulates OPC morphogenesis <em>in vivo</em>, supporting the role of the ECM in neural development.</div></div>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":"140 ","pages":"Article 100819"},"PeriodicalIF":2.2,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142683463","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 : 2024-11-01DOI: 10.1016/j.diff.2024.100816
Agathe Bouju , Roel Nusse , Peng V. Wu
Fibroblast Growth Factor 19 (FGF19) is a member of the Fibroblast Growth Factor (FGF) family, known for its role in various cellular processes including embryonic development and metabolic regulation. FGF19 functions as an endocrine factor, influencing energy balance, bile acid synthesis, glucose and lipid metabolism, as well as cell proliferation. FGF19 has a conserved structure typical of FGFs but exhibits unique features. Unlike most FGFs, which act locally, FGF19 travels through the bloodstream to distant targets including the liver. Its interaction with the β-Klotho (KLB) co-receptor and FGF Receptor 4 (FGFR4) in hepatocytes or FGFR1c in extrahepatic tissues initiates signaling cascades crucial for its biological functions. Although the mouse ortholog, FGF15, diverges significantly from human FGF19 in protein sequence and receptor binding, studies of FGF15-deficient mice have led to a better understanding of the proteins’ role in bile acid regulation, metabolism, and embryonic development. Overexpression studies in transgenic mice have further revealed roles in not only ameliorating metabolic diseases but also in promoting hepatocyte proliferation and tumorigenesis. This review summarizes the gene and protein structure of FGF19/15, its expression patterns, phenotypes in mutant models, and implication in human diseases, providing insights into potential therapeutic strategies targeting the FGF19 signaling pathway.
{"title":"A primer on the pleiotropic endocrine fibroblast growth factor FGF19/FGF15","authors":"Agathe Bouju , Roel Nusse , Peng V. Wu","doi":"10.1016/j.diff.2024.100816","DOIUrl":"10.1016/j.diff.2024.100816","url":null,"abstract":"<div><div>Fibroblast Growth Factor 19 (FGF19) is a member of the Fibroblast Growth Factor (FGF) family, known for its role in various cellular processes including embryonic development and metabolic regulation. FGF19 functions as an endocrine factor, influencing energy balance, bile acid synthesis, glucose and lipid metabolism, as well as cell proliferation. FGF19 has a conserved structure typical of FGFs but exhibits unique features. Unlike most FGFs, which act locally, FGF19 travels through the bloodstream to distant targets including the liver. Its interaction with the β-Klotho (KLB) co-receptor and FGF Receptor 4 (FGFR4) in hepatocytes or FGFR1c in extrahepatic tissues initiates signaling cascades crucial for its biological functions. Although the mouse ortholog, FGF15, diverges significantly from human FGF19 in protein sequence and receptor binding, studies of FGF15-deficient mice have led to a better understanding of the proteins’ role in bile acid regulation, metabolism, and embryonic development. Overexpression studies in transgenic mice have further revealed roles in not only ameliorating metabolic diseases but also in promoting hepatocyte proliferation and tumorigenesis. This review summarizes the gene and protein structure of FGF19/15, its expression patterns, phenotypes in mutant models, and implication in human diseases, providing insights into potential therapeutic strategies targeting the FGF19 signaling pathway.</div></div>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":"140 ","pages":"Article 100816"},"PeriodicalIF":2.2,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142583566","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-01DOI: 10.1016/j.diff.2024.100817
Diana Rigueur
During the discovery of the Fibroblast Growth Factor superfamily, scientists were determined to uncover all the genes that encoded FGF proteins. In 1998, FGF16 was discovered with classical cloning techniques in human and rat heart samples. FGF16 loss- and gain-of-function experiments in several organisms demonstrated a conserved function in vertebrates, and as a component of the FGF9 subfamily of ligands (FGF-E/-9/-20), is functionally conserved and sufficient to rescue loss-of-function phenotypes in invertebrates, like C. elegans. FGF16 has a broad expression pattern, predominantly expressed in brown adipose tissue, heart, with low but detectable levels in the brain, olfactory bulb, inner ear, muscle, thymus, pancreas, spleen, stomach, small intestine, and gonads (testis and ovary). FGF16 is also expressed moderately in the late developing limb bud. Despite its expression levels, this ligand plays notable roles in autopod metacarpal development; loss of one allele causes congenital metacarpal 4–5 fusion and hand deformities in humans. The broad expression pattern of FGF16 in several tissues underscores its multifaceted roles in stem cell maintenance, proliferation, cell fate specification, and metabolism.
{"title":"A primer for Fibroblast Growth Factor 16 (FGF16)","authors":"Diana Rigueur","doi":"10.1016/j.diff.2024.100817","DOIUrl":"10.1016/j.diff.2024.100817","url":null,"abstract":"<div><div>During the discovery of the Fibroblast Growth Factor superfamily, scientists were determined to uncover all the genes that encoded FGF proteins. In 1998, <em>FGF16</em> was discovered with classical cloning techniques in human and rat heart samples. <em>FGF16</em> loss- and gain-of-function experiments in several organisms demonstrated a conserved function in vertebrates, and as a component of the FGF9 subfamily of ligands (FGF-E/-9/-20), is functionally conserved and sufficient to rescue loss-of-function phenotypes in invertebrates, like <em>C. elegans</em>. <em>FGF16</em> has a broad expression pattern, predominantly expressed in brown adipose tissue, heart, with low but detectable levels in the brain, olfactory bulb, inner ear, muscle, thymus, pancreas, spleen, stomach, small intestine, and gonads (testis and ovary). FGF16 is also expressed moderately in the late developing limb bud. Despite its expression levels, this ligand plays notable roles in autopod metacarpal development; loss of one allele causes congenital metacarpal 4–5 fusion and hand deformities in humans. The broad expression pattern of <em>FGF16</em> in several tissues underscores its multifaceted roles in stem cell maintenance, proliferation, cell fate specification, and metabolism.</div></div>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":"140 ","pages":"Article 100817"},"PeriodicalIF":2.2,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142781755","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Retinoblastoma protein is central in signaling networks of fundamental cell decisions such as proliferation and differentiation in all metazoans and cancer development. Immunostaining and biochemical evidence demonstrated that during interphase retinoblastoma protein is in the nucleus and is hypophosphorylated, and during mitosis is in the cytoplasm and is hyperphosphorylated. The purpose of this study was to visualize in vivo in a non-diseased tissue, the dynamic spatial and temporal nuclear exit toward the cytoplasm of this protein during mitosis and its return to the nucleus to obtain insights into its potential cytosolic functions. Using high-resolution time-lapse images from confocal microscopy, we tracked in vivo the ortholog in plants the RETINOBLASTOMA RELATED (RBR) protein tagged with Green Fluorescent Protein (GFP) in Arabidopsis thaliana's root. RBR protein exits from dense aggregates in the nucleus before chromosomes are in prophase in less than 2 min, spreading outwards as smaller particles projected throughout the cytosol during mitosis like a diffusive yet controlled event until telophase, when the daughter's nuclei form; RBR returns to the nuclei in coordination with decondensing chromosomal DNA forming new aggregates again in punctuated larger structures in each corresponding nuclei. We propose RBR diffused particles in the cytoplasm may function as a cytosolic sensor of incoming signals, thus coordinating re-aggregation with DNA is a mechanism by which any new incoming signals encountered by RBR may lead to a reconfiguration of the nuclear transcriptomic context. The small RBR diffused particles in the cytoplasm may preserve topologic-like properties allowing them to aggregate and restore their nuclear location, they may also be part of transient cytoplasmic storage of the cellular pre-mitotic transcriptional context, that once inside the nuclei may execute both the pre mitosis transcriptional context as well as new transcriptional instructions.
视网膜母细胞瘤蛋白在所有变态类动物的细胞增殖和分化以及癌症发展等基本细胞决定的信号网络中起着核心作用。免疫染色和生化证据表明，在细胞间期，视网膜母细胞瘤蛋白位于细胞核内，磷酸化程度低；而在有丝分裂期，视网膜母细胞瘤蛋白位于细胞质内，磷酸化程度高。本研究的目的是在非病变组织中，在体内观察该蛋白在有丝分裂过程中向细胞质的动态空间和时间核出口及其返回细胞核的过程，以深入了解其潜在的细胞膜功能。利用共聚焦显微镜拍摄的高分辨率延时图像，我们在拟南芥根部追踪了植物中的同源物--标记有绿色荧光蛋白（GFP）的RETINOBLASTOMA RELATED（RBR）蛋白。RBR 蛋白在染色体进入前期前不到 2 分钟就从细胞核的致密聚集体中流出，在有丝分裂过程中以更小的颗粒向外扩散，投射到整个细胞质中，就像一个扩散但可控的事件，直到端期，当子核形成时；RBR 与染色体 DNA 的解聚协调返回细胞核，在每个相应的细胞核中再次形成新的聚集体，形成点状的更大的结构。我们认为，细胞质中的 RBR 扩散颗粒可能充当了传入信号的细胞传感器，因此与 DNA 的重新聚集协调是一种机制，RBR 遇到的任何新传入信号都可能导致核转录组背景的重新配置。细胞质中扩散的 RBR 小颗粒可能保留了类似拓扑学的特性，使其能够聚集并恢复其核位置，它们也可能是细胞质中瞬时储存的有丝分裂前转录背景的一部分，一旦进入细胞核，就可能执行有丝分裂前转录背景以及新的转录指令。
{"title":"In vivo movement of retinoblastoma-related protein (RBR) towards cytoplasm during mitosis in Arabidopsis thaliana","authors":"Sergio Miguel-Hernández , Estephania Zluhan-Martínez , Adriana Garay-Arroyo , Lourdes Cabrera-Muñoz , Adriana Hernández-Angeles , Noé Valentín Durán-Figueroa , Vadim Pérez-Koldenkova , M. Verónica Ponce-Castañeda","doi":"10.1016/j.diff.2024.100800","DOIUrl":"10.1016/j.diff.2024.100800","url":null,"abstract":"<div><div><span><span><span>Retinoblastoma protein<span> is central in signaling networks of fundamental cell decisions such as proliferation and differentiation in all metazoans and cancer development. </span></span>Immunostaining and biochemical evidence demonstrated that during </span>interphase retinoblastoma protein is in the nucleus and is hypophosphorylated, and during mitosis is in the cytoplasm and is hyperphosphorylated. The purpose of this study was to visualize </span><em>in vivo</em><span> in a non-diseased tissue, the dynamic spatial and temporal nuclear exit toward the cytoplasm of this protein during mitosis and its return to the nucleus to obtain insights into its potential cytosolic functions. Using high-resolution time-lapse images from confocal microscopy, we tracked </span><em>in vivo</em><span> the ortholog in plants the RETINOBLASTOMA RELATED (RBR) protein tagged with Green Fluorescent Protein (GFP) in </span><span><span>Arabidopsis thaliana</span></span><span><span>'s root. RBR protein exits from dense aggregates in the nucleus before chromosomes are in </span>prophase<span> in less than 2 min, spreading outwards as smaller particles projected throughout the cytosol during mitosis like a diffusive yet controlled event until telophase<span>, when the daughter's nuclei form; RBR returns to the nuclei in coordination with decondensing chromosomal DNA forming new aggregates again in punctuated larger structures in each corresponding nuclei. We propose RBR diffused particles in the cytoplasm may function as a cytosolic sensor of incoming signals, thus coordinating re-aggregation with DNA is a mechanism by which any new incoming signals encountered by RBR may lead to a reconfiguration of the nuclear transcriptomic context. The small RBR diffused particles in the cytoplasm may preserve topologic-like properties allowing them to aggregate and restore their nuclear location, they may also be part of transient cytoplasmic storage of the cellular pre-mitotic transcriptional context, that once inside the nuclei may execute both the pre mitosis transcriptional context as well as new transcriptional instructions.</span></span></span></div></div>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":"140 ","pages":"Article 100800"},"PeriodicalIF":2.2,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141581446","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}
Osteogenic differentiation is a crucial process in the formation of the skeleton and the remodeling of bones. It relies on a complex system of signaling pathways and transcription factors, including Runt-related transcription factor 2 (RUNX2). Non-coding RNAs (ncRNAs) control the bone-specific transcription factor RUNX2 through post-transcriptional mechanisms to regulate osteogenic differentiation. The most research has focused on microRNAs (miRNAs) and long ncRNAs (lncRNAs) in studying how they regulate RUNX2 for osteogenesis in both normal and pathological situations. This article provides a concise overview of the recent advancements in understanding the critical roles of lncRNA/miRNA/axes in controlling the expression of RUNX2 during bone formation. The possible application of miRNAs and lncRNAs as therapeutic agents for the treatment of disorders involving the bones and bones itself is also covered.
{"title":"RUNX2 regulation in osteoblast differentiation: A possible therapeutic function of the lncRNA and miRNA-mediated network","authors":"Pakkath Narayanan Arya, Iyyappan Saranya, Nagarajan Selvamurugan","doi":"10.1016/j.diff.2024.100803","DOIUrl":"10.1016/j.diff.2024.100803","url":null,"abstract":"<div><div>Osteogenic differentiation is a crucial process in the formation of the skeleton and the remodeling of bones. It relies on a complex system of signaling pathways and transcription factors, including Runt-related transcription factor 2 (RUNX2). Non-coding RNAs (ncRNAs) control the bone-specific transcription factor RUNX2 through post-transcriptional mechanisms to regulate osteogenic differentiation. The most research has focused on microRNAs (miRNAs) and long ncRNAs (lncRNAs) in studying how they regulate RUNX2 for osteogenesis in both normal and pathological situations. This article provides a concise overview of the recent advancements in understanding the critical roles of lncRNA/miRNA/axes in controlling the expression of RUNX2 during bone formation. The possible application of miRNAs and lncRNAs as therapeutic agents for the treatment of disorders involving the bones and bones itself is also covered.</div></div>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":"140 ","pages":"Article 100803"},"PeriodicalIF":2.2,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141848584","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 : 2024-11-01DOI: 10.1016/j.diff.2024.100813
Zane Oberholzer, Chiron Loubser, Natalya V. Nikitina
The Fibroblast growth factor (FGFs) family consists of at least 22 members that exert their function by binding and activating fibroblast growth factor receptors (FGFRs). The Fgf8/FgfD subfamily member, Fgf17, is located on human chromosome 8p21.3 and mouse chromosome 14 D2. In humans, FGF17 can be alternatively spliced to produce two isoforms (FGF17a and b) whereas three isoforms are present in mice (Fgf17a, b, and c), however, only Fgf17a and Fgf17b produce functional proteins. Fgf17 is a secreted protein with a cleavable N-terminal signal peptide and contains two binding domains, namely a conserved core region and a heparin binding site. Fgf17 mRNA is expressed in a wide range of different tissues during development, including the rostral patterning centre, midbrain-hindbrain boundary, tailbud mesoderm, olfactory placode, mammary glands, and smooth muscle precursors of major arteries. Given its broad expression pattern during development, it is surprising that adult Fgf17−/− mice displayed a rather mild phenotype; such that mutants only exhibited morphological changes in the frontal cortex and mid/hind brain boundary and changes in certain social behaviours. In humans, FGF17 mutations are implicated in several diseases, including Congenital Hypogonadotropic Hypogonadism and Kallmann Syndrome. FGF17 mutations contribute to CHH/KS in 1.1% of affected individuals, often presenting in conjunction with mutations in other FGF pathway genes like FGFR1 and FLRT3. FGF17 mutations were also identified in patients diagnosed with Dandy-Walker malformation and Pituitary Stalk Interruption Syndrome, however, it remains unclear how FGF17 is implicated in these diseases. Altered FGF17 expression has been observed in several cancers, including prostate cancer, hematopoietic cancers (acute myeloid leukemia and acute lymphoblastic leukemia), glioblastomas, perineural invasion in cervical cancer, and renal cell carcinomas. Furthermore, FGF17 has demonstrated neuroprotective effects, particularly during ischemic stroke, and has been shown to improve cognitive function in ageing mice.
{"title":"Fgf17: A regulator of the mid/hind brain boundary in mammals","authors":"Zane Oberholzer, Chiron Loubser, Natalya V. Nikitina","doi":"10.1016/j.diff.2024.100813","DOIUrl":"10.1016/j.diff.2024.100813","url":null,"abstract":"<div><div>The Fibroblast growth factor (FGFs) family consists of at least 22 members that exert their function by binding and activating fibroblast growth factor receptors (FGFRs). The <em>Fgf8/FgfD</em> subfamily member, <em>Fgf17</em>, is located on human chromosome 8p21.3 and mouse chromosome 14 D2. In humans, FGF17 can be alternatively spliced to produce two isoforms (FGF17a and b) whereas three isoforms are present in mice (Fgf17a, b, and c), however, only Fgf17a and Fgf17b produce functional proteins. Fgf17 is a secreted protein with a cleavable N-terminal signal peptide and contains two binding domains, namely a conserved core region and a heparin binding site. <em>Fgf1</em>7 mRNA is expressed in a wide range of different tissues during development, including the rostral patterning centre, midbrain-hindbrain boundary, tailbud mesoderm, olfactory placode, mammary glands, and smooth muscle precursors of major arteries. Given its broad expression pattern during development, it is surprising that adult <em>Fgf17</em><sup><em>−/−</em></sup> mice displayed a rather mild phenotype; such that mutants only exhibited morphological changes in the frontal cortex and mid/hind brain boundary and changes in certain social behaviours. In humans, <em>FGF17</em> mutations are implicated in several diseases, including Congenital Hypogonadotropic Hypogonadism and Kallmann Syndrome. <em>FGF17</em> mutations contribute to CHH/KS in 1.1% of affected individuals, often presenting in conjunction with mutations in other <em>FGF</em> pathway genes like <em>FGFR1</em> and <em>FLRT3</em>. <em>FGF17</em> mutations were also identified in patients diagnosed with Dandy-Walker malformation and Pituitary Stalk Interruption Syndrome, however, it remains unclear how <em>FGF17</em> is implicated in these diseases. Altered <em>FGF17</em> expression has been observed in several cancers, including prostate cancer, hematopoietic cancers (acute myeloid leukemia and acute lymphoblastic leukemia), glioblastomas, perineural invasion in cervical cancer, and renal cell carcinomas. Furthermore, FGF17 has demonstrated neuroprotective effects, particularly during ischemic stroke, and has been shown to improve cognitive function in ageing mice.</div></div>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":"140 ","pages":"Article 100813"},"PeriodicalIF":2.2,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142331690","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-01DOI: 10.1016/j.diff.2024.100814
Lucia J. Rivas , Rosa A. Uribe
Fibroblast Growth Factor (FGF) 13, also referred to as FGF homologous factor (FHF) 2, is a member of the FGF11 subfamily that is characterized as having sequence similarities to classical FGF receptor (FGFR)-binding FGFs, but functionally do not bind FGFRs. In this primer mini-review, we summarize current knowledge regarding FGF13 expression, mutant analyses, and gene and protein structure. Similar to other FHFs, FGF13 has been considered a non-secreted protein that lacks an amino signal and is prominently expressed in developing and mature neurons of the central and peripheral nervous systems, as well as the heart. The expression of FGF13 is not limited to early embryonic stages and has been shown to persist in adult tissues. As well, FGF13 is known to localize subcellularly, both within the cytoplasm and the nucleus. FGF13 is extremely adaptable, as it interacts with MAPK scaffolding protein islet brain 2 (IB2), stabilizes microtubules, or binds to voltage-gated sodium channels. Fgf13 mutant mouse lines display various neurological pathologies. Through sequence mapping, FGF13 is considered a candidate causative gene that is mutated in multiple human X-linked neurological diseases.
{"title":"Fibroblast Growth Factor (FGF) 13","authors":"Lucia J. Rivas , Rosa A. Uribe","doi":"10.1016/j.diff.2024.100814","DOIUrl":"10.1016/j.diff.2024.100814","url":null,"abstract":"<div><div>Fibroblast Growth Factor (FGF) 13, also referred to as FGF homologous factor (FHF) 2, is a member of the FGF11 subfamily that is characterized as having sequence similarities to classical FGF receptor (FGFR)-binding FGFs, but functionally do not bind FGFRs. In this primer mini-review, we summarize current knowledge regarding FGF13 expression, mutant analyses, and gene and protein structure. Similar to other FHFs, FGF13 has been considered a non-secreted protein that lacks an amino signal and is prominently expressed in developing and mature neurons of the central and peripheral nervous systems, as well as the heart. The expression of FGF13 is not limited to early embryonic stages and has been shown to persist in adult tissues. As well, FGF13 is known to localize subcellularly, both within the cytoplasm and the nucleus. FGF13 is extremely adaptable, as it interacts with MAPK scaffolding protein islet brain 2 (IB2), stabilizes microtubules, or binds to voltage-gated sodium channels. <em>Fgf13</em> mutant mouse lines display various neurological pathologies. Through sequence mapping, <em>FGF13</em> is considered a candidate causative gene that is mutated in multiple human X-linked neurological diseases.</div></div>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":"140 ","pages":"Article 100814"},"PeriodicalIF":2.2,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142331691","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}
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