Differentiation最新文献

{"title":"The ciliary protein C2cd3 is required for mandibular musculoskeletal tissue patterning","authors":"Evan C. Brooks ,&nbsp;Simon J.Y. Han ,&nbsp;Christian Louis Bonatto Paese ,&nbsp;Amya A. Lewis ,&nbsp;Megan Aarnio-Peterson ,&nbsp;Samantha A. Brugmann","doi":"10.1016/j.diff.2024.100782","DOIUrl":"10.1016/j.diff.2024.100782","url":null,"abstract":"<div><p>The mandible is composed of several musculoskeletal tissues including bone, cartilage, and tendon that require precise patterning to ensure structural and functional integrity. Interestingly, most of these tissues are derived from one multipotent cell population called cranial neural crest cells (CNCCs). How CNCCs are properly instructed to differentiate into various tissue types remains nebulous. To better understand the mechanisms necessary for the patterning of mandibular musculoskeletal tissues we utilized the avian mutant <em>talpid</em>^<em>2</em> (<em>ta</em>^<em>2</em>) which presents with several malformations of the facial skeleton including dysplastic tendons, mispatterned musculature, and bilateral ectopic cartilaginous processes extending off Meckel's cartilage. We found an ectopic epithelial BMP signaling domain in the <em>ta</em>^<em>2</em> mandibular prominence (MNP) that correlated with the subsequent expansion of <em>SOX9</em>+ cartilage precursors. These findings were validated with conditional murine models suggesting an evolutionarily conserved mechanism for CNCC-derived musculoskeletal patterning. Collectively, these data support a model in which cilia are required to define epithelial signal centers essential for proper musculoskeletal patterning of CNCC-derived mesenchyme.</p></div>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":"138 ","pages":"Article 100782"},"PeriodicalIF":2.9,"publicationDate":"2024-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0301468124000380/pdfft?md5=5f039bdd425a7be72f18daf3f8a996ae&pid=1-s2.0-S0301468124000380-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141176790","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":"Pax6 isoforms shape eye development: Insights from developmental stages and organoid models","authors":"Shih-Shun Hung ,&nbsp;Po-Sung Tsai ,&nbsp;Ching-Wen Po ,&nbsp;Pei-Shan Hou","doi":"10.1016/j.diff.2024.100781","DOIUrl":"https://doi.org/10.1016/j.diff.2024.100781","url":null,"abstract":"<div><p>Pax6 is a critical transcription factor involved in the development of the central nervous system. However, in humans, mutations in Pax6 predominantly result in iris deficiency rather than neurological phenotypes. This may be attributed to the distinct functions of Pax6 isoforms, <em>Pax6a</em> and <em>Pax6b</em>. In this study, we investigated the spatial and temporal expression patterns of Pax6 isoforms during different stages of mouse eye development. We observed a strong correlation between <em>Pax6a</em> expression and the neuroretina gene <em>Sox2</em>, while <em>Pax6b</em> showed a high correlation with iris-component genes, including the mesenchymal gene <em>Foxc1</em>. During early patterning from E10.5, <em>Pax6b</em> was expressed in the hinge of the optic cup and neighboring mesenchymal cells, whereas <em>Pax6a</em> was absent in these regions. At E14.5, both <em>Pax6a</em> and <em>Pax6b</em> were expressed in the future iris and ciliary body, coinciding with the integration of mesenchymal cells and <em>Mitf</em>-positive cells in the outer region. From E18.5, Pax6 isoforms exhibited distinct expression patterns as lineage genes became more restricted. To further validate these findings, we utilized ESC-derived eye organoids, which recapitulated the temporal and spatial expression patterns of lineage genes and Pax6 isoforms. Additionally, we found that the spatial expression patterns of <em>Foxc1</em> and <em>Mitf</em> were impaired in <em>Pax6b</em>-mutant ESC-derived eye organoids. This in vitro eye organoids model suggested the involvement of <em>Pax6b</em>-positive local mesodermal cells in iris development. These results provide valuable insights into the regulatory roles of Pax6 isoforms during iris and neuroretina development and highlight the potential of ESC-derived eye organoids as a tool for studying normal and pathological eye development.</p></div>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":"137 ","pages":"Article 100781"},"PeriodicalIF":2.9,"publicationDate":"2024-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0301468124000379/pdfft?md5=8e67d792469eac5c4ece7d22329136d5&pid=1-s2.0-S0301468124000379-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140555556","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":"Fibroblast Growth Factor 6","authors":"Jennelle Smith ,&nbsp;Loydie A. Jerome-Majewska","doi":"10.1016/j.diff.2024.100780","DOIUrl":"https://doi.org/10.1016/j.diff.2024.100780","url":null,"abstract":"<div><p>Fibroblast Growth Factor 6 (<em>FGF6</em>), also referred to as <em>HST2</em> or <em>HBGF6</em>, is a member of the Fibroblast Growth Factor (FGF), the Heparin Binding Growth Factor (HBGF) and the Heparin Binding Secretory Transforming Gene (HST) families. The genomic and protein structure of FGF6 is highly conserved among varied species, as is its expression in muscle and muscle progenitor cells. Like other members of the FGF family, <em>FGF6</em> regulates cell proliferation, differentiation, and migration. Specifically, it plays key roles in myogenesis and muscular regeneration, angiogenesis, along with iron transport and lipid metabolism. Similar to others from the FGF family, <em>FGF6</em> also possesses oncogenic transforming activity, and as such is implicated in a variety of cancers.</p></div>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":"137 ","pages":"Article 100780"},"PeriodicalIF":2.9,"publicationDate":"2024-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0301468124000367/pdfft?md5=cfbe55726f20d1e1270ee44f3c9772ab&pid=1-s2.0-S0301468124000367-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140552481","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":"Cell cycle perturbation uncouples mitotic progression and invasive behavior in a post-mitotic cell","authors":"Michael A.Q. Martinez ,&nbsp;Chris Z. Zhao ,&nbsp;Frances E.Q. Moore ,&nbsp;Callista Yee ,&nbsp;Wan Zhang ,&nbsp;Kang Shen ,&nbsp;Benjamin L. Martin ,&nbsp;David Q. Matus","doi":"10.1016/j.diff.2024.100765","DOIUrl":"10.1016/j.diff.2024.100765","url":null,"abstract":"<div><p>The acquisition of the post-mitotic state is crucial for the execution of many terminally differentiated cell behaviors during organismal development. However, the mechanisms that maintain the post-mitotic state in this context remain poorly understood. To gain insight into these mechanisms, we used the genetically and visually accessible model of <em>C. elegans</em> anchor cell (AC) invasion into the vulval epithelium. The AC is a terminally differentiated uterine cell that normally exits the cell cycle and enters a post-mitotic state before initiating contact between the uterus and vulva through a cell invasion event. Here, we set out to identify the set of negative cell cycle regulators that maintain the AC in this post-mitotic, invasive state. Our findings revealed a critical role for CKI-1 (p21^CIP1/p27^KIP1) in redundantly maintaining the post-mitotic state of the AC, as loss of CKI-1 in combination with other negative cell cycle regulators—including CKI-2 (p21^CIP1/p27^KIP1), LIN-35 (pRb/p107/p130), FZR-1 (Cdh1/Hct1), and LIN-23 (β-TrCP)—resulted in proliferating ACs. Remarkably, time-lapse imaging revealed that these ACs retain their ability to invade. Upon examination of a node in the gene regulatory network controlling AC invasion, we determined that proliferating, invasive ACs do so by maintaining aspects of pro-invasive gene expression. We therefore report that the requirement for a post-mitotic state for invasive cell behavior can be bypassed following direct cell cycle perturbation.</p></div>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":"137 ","pages":"Article 100765"},"PeriodicalIF":2.9,"publicationDate":"2024-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140148321","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":"Type 1 collagen: Synthesis, structure and key functions in bone mineralization","authors":"Vimalraj Selvaraj ,&nbsp;Saravanan Sekaran ,&nbsp;Anuradha Dhanasekaran ,&nbsp;Sudha Warrier","doi":"10.1016/j.diff.2024.100757","DOIUrl":"10.1016/j.diff.2024.100757","url":null,"abstract":"<div><p>Collagen is a highly abundant protein in the extracellular matrix of humans and mammals, and it plays a critical role in maintaining the body's structural integrity. Type I collagen is the most prevalent collagen type and is essential for the structural integrity of various tissues. It is present in nearly all connective tissues and is the main constituent of the interstitial matrix. Mutations that affect collagen fiber formation, structure, and function can result in various bone pathologies, underscoring the significance of collagen in sustaining healthy bone tissue. Studies on type 1 collagen have revealed that mutations in its encoding gene can lead to diverse bone diseases, such as osteogenesis imperfecta, a disorder characterized by fragile bones that are susceptible to fractures. Knowledge of collagen's molecular structure, synthesis, assembly, and breakdown is vital for comprehending embryonic and foetal development and several aspects of human physiology. In this review, we summarize the structure, molecular biology of type 1 collagen, its biomineralization and pathologies affecting bone.</p></div>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":"136 ","pages":"Article 100757"},"PeriodicalIF":2.9,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140009594","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":"Oxidative-stress induced Bmp2-Smad1/5/8 signaling dependent differentiation of early cardiomyocytes from embryonic and adult epicardial cells","authors":"Madhurima Ghosh ,&nbsp;Riffat Khanam ,&nbsp;Arunima Sengupta ,&nbsp;Santanu Chakraborty","doi":"10.1016/j.diff.2024.100756","DOIUrl":"10.1016/j.diff.2024.100756","url":null,"abstract":"<div><p>Heart failure has become a major life-threatening cause affecting millions globally, characterized by the permanent loss of adult functional cardiomyocytes leading to fibrosis which ultimately deprives the heart of its functional efficacy. Here we investigated the reparative property of embryonic and adult epicardial cells towards cardiomyocyte differentiation under oxidative stress-induced conditions along with the identification of a possible molecular signaling pathway. Isolated epicardial cells from embryonic chick hearts subjected to oxidative stress and hypoxia induction. Initial assessment of successful injury induction reveals hypertrophy of isolated epicardial cells. Detailed marker gene expression analyses and inhibitor studies reveal Bone morphogenic protein (Bmp)2-Smad1/5/8 signaling dependent cardiomyocyte lineage specification via epithelial to mesenchymal transition (EMT) post-injury. EMT is further confirmed by increased proliferation, migration, and differentiation towards cardiomyocyte lineage. We have also established an <em>in-vivo</em> model in adult male rats using Isoproterenol. Successful oxidative stress-mediated injury induction in adult heart was marked by increased activated fibroblasts followed by apoptosis of adult cardiomyocytes. The detailed characterization of adult epicardial cells reveals similar findings to our avian <em>in-vitro</em> data. Both <em>in-vitro</em> and <em>in-vivo</em> results show a significant increase in the expression of cardiomyocyte specific markers indicative of lineage specificity and activation of epicardial cells post oxidative stress mediated injury. Our findings suggest an EMT-induced reactivation of epicardial cells and early cardiomyocyte lineage specification following oxidative stress in a Bmp2- Smad1/5/8 dependent manner. Overall, this regulatory mechanism of cardiomyocyte differentiation induced by oxidative stress may contribute to the field of cardiac repair and regenerative therapeutics.</p></div>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":"136 ","pages":"Article 100756"},"PeriodicalIF":2.9,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140054043","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":"The road to gene manipulation in the mouse: Jean Brachet Memorial Lecture of the International Society of Differentiation (delivered June 21, 2023 at Cold Spring Harbor Laboratory)","authors":"Virginia Papaioannou PhD","doi":"10.1016/j.diff.2024.100753","DOIUrl":"10.1016/j.diff.2024.100753","url":null,"abstract":"<div><p>Genetic manipulation in mammals has progressed rapidly in the past decade with the advent of CRISPR-Cas gene editing tools, promising profound impacts on the understanding of human development, health and disease. However, many years of research in divergent fields of experimental embryology, genetics, reproduction, molecular biology and transgenic technology laid the groundwork and have played critical roles for this progress. This article details various threads of research and the central role of the laboratory mouse that came together in reaching this point, all from the perspective of a scientist whose research was deeply immersed in the field.</p></div>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":"136 ","pages":"Article 100753"},"PeriodicalIF":2.9,"publicationDate":"2024-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139589058","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 adipogenesis by histone methyltransferases","authors":"Yuanxiang Zhao ,&nbsp;Zachary Skovgaard ,&nbsp;Qinyi Wang","doi":"10.1016/j.diff.2024.100746","DOIUrl":"10.1016/j.diff.2024.100746","url":null,"abstract":"<div><p>Epigenetic regulation is a critical component of lineage determination. Adipogenesis is the process through which uncommitted stem cells or adipogenic precursor cells differentiate into adipocytes, the most abundant cell type of the adipose tissue. Studies examining chromatin modification during adipogenesis have provided further understanding of the molecular blueprint that controls the onset of adipogenic differentiation. Unlike histone acetylation, histone methylation has context dependent effects on the activity of a transcribed region of DNA, with individual or combined marks on different histone residues providing distinct signals for gene expression. Over half of the 42 histone methyltransferases identified in mammalian cells have been investigated in their role during adipogenesis, but across the large body of literature available, there is a lack of clarity over potential correlations or emerging patterns among the different players. In this review, we will summarize important findings from studies published in the past 15 years that have investigated the role of histone methyltransferases during adipogenesis, including both protein arginine methyltransferases (PRMTs) and lysine methyltransferases (KMTs). We further reveal that PRMT1/4/5, H3K4 KMTs (MLL1, MLL3, MLL4, SMYD2 and SET7/9) and H3K27 KMTs (EZH2) all play positive roles during adipogenesis, while PRMT6/7 and H3K9 KMTs (G9a, SUV39H1, SUV39H2, and SETDB1) play negative roles during adipogenesis.</p></div>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":"136 ","pages":"Article 100746"},"PeriodicalIF":2.9,"publicationDate":"2024-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0301468124000021/pdfft?md5=4d52ee29c3658350512006682d1fb712&pid=1-s2.0-S0301468124000021-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139469352","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":"BBS genes are involved in accelerated proliferation and early differentiation of BBS-related tissues","authors":"Avital Horwitz ,&nbsp;Noa Levi-Carmel ,&nbsp;Olga Shnaider ,&nbsp;Ruth Birk","doi":"10.1016/j.diff.2024.100745","DOIUrl":"10.1016/j.diff.2024.100745","url":null,"abstract":"<div><p>Bardet-Biedl syndrome (BBS) is an inherited disorder primarily ciliopathy with pleiotropic multi-systemic phenotypic involvement, including adipose, nerve, retinal, kidney, Etc. Consequently, it is characterized by obesity, cognitive impairment and retinal, kidney and cutaneous abnormalities. Initial studies, including ours have shown that <em>BBS</em> genes play a role in the early developmental stages of adipocytes and β-cells. However, this role in other BBS-related tissues is unknown.</p><p>We investigated <em>BBS</em> genes involvement in the proliferation and early differentiation of different BBS cell types.</p><p>The involvement of <em>BBS</em><span> genes in cellular proliferation were studied in seven </span><em>in-vitro</em><span><span> and transgenic cell models; </span>keratinocytes (</span><em>hHaCaT</em>) and Ras-transfected keratinocytes (<em>Ras-hHaCaT</em>), neuronal cell lines (<em>hSH-SY5Y</em> and <em>rPC-12</em>), silenced <span><em>BBS4</em></span> neural cell lines (s<em>iBbs4 hSH-SY5Y</em> and <em>siBbs4 rPC-12</em>), adipocytes (<em>m3T3L1</em>), and <em>ex-vivo</em> transformed B-cells obtain from <em>BBS4</em> patients, using molecular and biochemical methodologies.</p><p><em>RashHaCaT</em> cells showed an accelerated proliferation rate in parallel to significant reduction in the transcript levels of <span><em>BBS1</em><em>, 2</em></span>, and <em>4</em>. <em>BBS1, 2, and 4</em> transcripts linked with <em>hHaCaT</em><span> cell cycle arrest (G1 phase) using both chemical (CDK4 inhibitor) and serum deprivation methodologies. Adipocyte (</span><em>m3T3-L1</em>) <em>Bbs1, 2</em> and <em>4</em><span> transcript levels corresponded to the cell cycle phase (CDK4 inhibitor and serum deprivation). </span><em>SiBBS4 hSH-SY5Y</em> cells exhibited early cell proliferation and differentiation (wound healing assay) rates. <em>SiBbs4 rPC-12</em> models exhibited significant proliferation and differentiation rate corresponding to Nestin expression levels. <em>BBS4</em> patients-transformed B-cells exhibited an accelerated proliferation rate (LPS-induced methodology).</p><p>In conclusions, the <em>BBS4</em> gene plays a significant, similar and global role in the cellular proliferation of various BBS related tissues. These results highlight the universal role of the BBS gene in the cell cycle, and further deepen the knowledge of the mechanisms underlying the development of BBS.</p></div>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":"135 ","pages":"Article 100745"},"PeriodicalIF":2.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139375767","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":"Ovotesticular cords and ovotesticular follicles: New markers in a model of human mixed ovotestis","authors":"Laurence Baskin,&nbsp;Mei Cao,&nbsp;Sena Askel,&nbsp;Yi Li,&nbsp;Gerald Cunha","doi":"10.1016/j.diff.2023.11.002","DOIUrl":"10.1016/j.diff.2023.11.002","url":null,"abstract":"","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":"135 ","pages":"Article 100739"},"PeriodicalIF":2.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0301468123000786/pdfft?md5=b1eae3a9d5f4d791ad58e0a4d047f69f&pid=1-s2.0-S0301468123000786-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138435410","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}