Differentiation最新文献

{"title":"Are vagal neural crest derived tissues impacted in spliceosomopathies?","authors":"Joshua A. Moore ,&nbsp;Loydie A. Jerome-Majewska","doi":"10.1016/j.diff.2025.100846","DOIUrl":"10.1016/j.diff.2025.100846","url":null,"abstract":"<div><div>Splicing factors required for mRNA maturation have emerged as important contributors to neural crest development in the craniofacial region. Less is known of the role of these proteins in vagal neural crest cells that contribute to the outflow tract and form the enteric nervous system. In this review, we discuss the current state of our understanding of splicing and potential contribution of mis-splicing to cardiac and ENS defects.</div></div>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":"142 ","pages":"Article 100846"},"PeriodicalIF":2.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143587752","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}

{"title":"NOTCH1, 2, and 3 receptors enhance osteoblastogenesis of mesenchymal C3H10T1/2 cells and inhibit this process in preosteoblastic MC3T3-E1 cells","authors":"Jose-Luis Resuela-González ,&nbsp;María-Julia González-Gómez ,&nbsp;María-Milagros Rodríguez-Cano ,&nbsp;Susana López-López ,&nbsp;Eva-María Monsalve ,&nbsp;María-José M. Díaz-Guerra ,&nbsp;Jorge Laborda ,&nbsp;María-Luisa Nueda ,&nbsp;Victoriano Baladrón","doi":"10.1016/j.diff.2025.100837","DOIUrl":"10.1016/j.diff.2025.100837","url":null,"abstract":"<div><div>Osteoblastogenesis is governed by complex interplays among signaling pathways, which modulate the expression of specific markers at each differentiation stage. This process enables osteoblast precursor cells to adopt the morphological and biochemical characteristics of mature bone cells. Our study investigates the role of NOTCH signaling in osteogenesis in MC3T3-E1 and C3H10T1/2 cell lines. MC3T3-E1 cells are preosteoblast precursors widely recognized as a model for bone biology research, offering a convenient and physiologically relevant system to study osteoblast transcriptional regulation. Conversely, the mesenchymal C3H10T1/2 cells are multipotent, capable of differentiating into osteoblasts, adipocytes, and chondrocytes under specific extracellular cues.</div><div>The core of this <em>in vitro</em> study is the comparative analysis of the impact of overexpressing each mammalian NOTCH receptor on osteoblastogenesis in two cell lines reflecting different cell differentiation stages. We generated stable transfectant pools of both cell lines for each of the four NOTCH receptors and characterized their effect on osteoblastogenesis. We successfully obtained transfectant pools that overexpress <em>Notch1</em>, <em>Notch2</em> and <em>Notch3</em> at both mRNA and protein levels. However, we were unable to obtain cells overexpressing <em>Notch4</em> at protein level. Our findings reveal that the overexpression of NOTCH1, NOTCH2, and NOTCH3 receptors promotes osteoblast differentiation in mesenchymal C3H10T1/2 cells, while inhibiting it in preosteoblastic MC3T3-E1 cells. These results provide novel insights into the distinct roles of NOTCH receptors in osteoblastogenesis across two different precursor cell types, potentially guiding the development of new therapeutic approaches for bone diseases.</div></div>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":"142 ","pages":"Article 100837"},"PeriodicalIF":2.2,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143069356","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}

{"title":"Divergent functions of the evolutionarily conserved, yet seemingly dispensable, Wnt target, sp5","authors":"Saurav Mohanty,&nbsp;Arne C. Lekven","doi":"10.1016/j.diff.2024.100829","DOIUrl":"10.1016/j.diff.2024.100829","url":null,"abstract":"<div><div>The activation of <em>sp5</em> in response to Wnt/β-catenin signaling is observed in many species during axis patterning, neural crest induction, maintenance and differentiation of stem cells. Indeed, the conserved response of <em>sp5</em> orthologs to Wnt-mediated activation is the basis for this gene commonly being used as a readout for Wnt signaling activity. However, several seemingly conflicting findings regarding the function of <em>sp5</em> in the context of Wnt signaling cast this gene in an enigmatic light. In this review, we examine current knowledge of <em>sp5</em> structure and function, its relationship to Wnt signaling in varied contexts, and present perspectives on how progress on this interesting gene can move forward.</div></div>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":"141 ","pages":"Article 100829"},"PeriodicalIF":2.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142830766","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}

{"title":"Regulation of trophectoderm morphogenesis by small GTPase RHOA through HIPPO signaling-dependent and -independent mechanisms in mouse preimplantation development","authors":"Yusuke Marikawa,&nbsp;Vernadeth B. Alarcon","doi":"10.1016/j.diff.2025.100835","DOIUrl":"10.1016/j.diff.2025.100835","url":null,"abstract":"<div><div>The trophectoderm (TE) is the first tissue to differentiate during the preimplantation development of the mammalian embryo. It forms the outer layer of the blastocyst and is responsible for generating the blastocoel, a fluid-filled cavity whose expansion is essential for successful hatching and implantation. Here, we investigated the role of the small GTPase RHOA in the morphogenesis of the TE, particularly its relationship with HIPPO signaling, using mouse embryos as a model. Inhibition of RHOA resulted in the failure to form a blastocoel and significantly altered the expression of numerous genes. Transcriptomic analysis revealed that 330 genes were down-regulated and 168 genes were up-regulated by more than two-fold. Notably, 98.4% of these transcriptional changes were reversed by simultaneous inhibition of LATS kinases, indicating that the transcriptional influence of RHOA is primarily mediated through HIPPO signaling. Many of the down-regulated genes are involved in critical processes of TE morphogenesis, such as apical-basal cell polarization, tight junction formation, and sodium and water transport, suggesting that RHOA supports TE development by enhancing the expression of morphogenesis-related genes through HIPPO signaling, specifically via TEAD transcription factors. However, RHOA inhibition also disrupted apical-basal polarity and tight junctions, effects that were not restored by LATS inhibition, pointing to additional HIPPO signaling-independent mechanisms by which RHOA controls TE morphogenesis. Furthermore, RHOA inhibition impaired cell viability at the late blastocyst stage, with partial rescue observed upon LATS inhibition, suggesting that RHOA maintains cell survival through both HIPPO signaling-dependent and -independent pathways. A deeper knowledge of the molecular mechanisms governing TE morphogenesis, including blastocoel expansion and cell viability, could significantly advance assisted reproductive technologies aimed at producing healthy blastocysts.</div></div>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":"141 ","pages":"Article 100835"},"PeriodicalIF":2.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143061334","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}

{"title":"NEDD4's effect on osteoblastogenesis potential of bone mesenchymal stem cells in rats concerned with PI3K/Akt pathway","authors":"Bo Li ,&nbsp;Shuang Zhang ,&nbsp;Xiaoxian Yun ,&nbsp;Chengyi Liu ,&nbsp;Rui Xiao ,&nbsp;Mingjie Lu ,&nbsp;Xiaomei Xu ,&nbsp;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}

{"title":"Deciphering endocrine function of adipose tissue and its significant influences in obesity-related diseases caused by its dysfunction","authors":"Feiyi Duan ,&nbsp;Jiaoyan Wu ,&nbsp;Jiayi Chang ,&nbsp;Haoyuan Peng ,&nbsp;Zitao Liu ,&nbsp;Pengfei Liu ,&nbsp;Xu Han ,&nbsp;Tiantian Sun ,&nbsp;Dandan Shang ,&nbsp;Yutian Yang ,&nbsp;Zhihao Li ,&nbsp;Pengkun Li ,&nbsp;Yixuan Liu ,&nbsp;Yonghao Zhu ,&nbsp;Yunzhi Lv ,&nbsp;Xiumei Guo ,&nbsp;Ying Zhao ,&nbsp;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}

{"title":"SMAD2/3 signaling determines the colony architecture in a hydrozoan, Dynamena pumila","authors":"Alexandra A. Vetrova ,&nbsp;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}

{"title":"Cspg4 sculpts oligodendrocyte precursor cell morphology","authors":"Samantha Bromley-Coolidge,&nbsp;Diego Iruegas,&nbsp;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}

{"title":"A primer on the pleiotropic endocrine fibroblast growth factor FGF19/FGF15","authors":"Agathe Bouju ,&nbsp;Roel Nusse ,&nbsp;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}

{"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}