Differentiation最新文献

{"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}

{"title":"Expression patterns of CYP26A1, FGF8, CDKN1A, and NPVF in the developing rhesus monkey retina","authors":"Miranda R. Krueger ,&nbsp;Elizabeth Fishman-Williams ,&nbsp;Sergi Simó ,&nbsp;Alice F. Tarantal ,&nbsp;Anna La Torre","doi":"10.1016/j.diff.2023.100743","DOIUrl":"10.1016/j.diff.2023.100743","url":null,"abstract":"<div><p>The <em>fovea centralis</em> (fovea) is a specialized region of the primate retina that plays crucial roles in high-resolution visual acuity and color perception. The fovea is characterized by a high density of cone photoreceptors and no rods, and unique anatomical properties that contribute to its remarkable visual capabilities. Early histological analyses identified some of the key events that contribute to foveal development, but the mechanisms that direct the specification of this area are not understood. Recently, the expression of the retinoic acid-metabolizing enzyme <em>CYP26A1</em> has become a hallmark of some of the retinal specializations found in vertebrates, including the primate fovea and the high-acuity area in avian species. In chickens, the retinoic acid pathway regulates the expression of <em>FGF8</em> to then direct the development of a rod-free area. Similarly, high levels of <em>CYP26A1, CDKN1A,</em> and <em>NPVF</em> expression have been observed in the primate macula using transcriptomic approaches. However, which retinal cells express these genes and their expression dynamics in the developing primate eye remain unknown. Here, we systematically characterize the expression patterns of <em>CYP26A1, FGF8, CDKN1A</em>, and <em>NPVF</em> during the development of the rhesus monkey retina, from early stages of development in the first trimester until the third trimester (near term). Our data suggest that some of the markers previously proposed to be fovea-specific are not enriched in the progenitors of the rhesus monkey fovea. In contrast, <em>CYP26A1</em> is expressed at high levels in the progenitors of the fovea, while it localizes in a subpopulation of macular Müller glia cells later in development. Together these data provide invaluable insights into the expression dynamics of several molecules in the nonhuman primate retina and highlight the developmental advancement of the foveal region.</p></div>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":"135 ","pages":"Article 100743"},"PeriodicalIF":2.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0301468123000919/pdfft?md5=016854dcce39621407be1f001cee6238&pid=1-s2.0-S0301468123000919-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138692940","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":"Network analysis of transcriptomic data uncovers molecular signatures and the interplay of mRNAs, lncRNAs, and miRNAs in human embryonic stem cells","authors":"Arindam Ghosh ,&nbsp;Anup Som","doi":"10.1016/j.diff.2023.11.001","DOIUrl":"10.1016/j.diff.2023.11.001","url":null,"abstract":"<div><p>Growing evidence has shown that besides the protein coding genes, the non-coding elements of the genome are indispensable for maintaining the property of self-renewal in human embryonic stem cells and in cell fate determination. However, the regulatory mechanisms and the landscape of interactions between the coding and non-coding elements is poorly understood. In this work, we used weighted gene co-expression network analysis (WGCNA) on transcriptomic data retrieved from RNA-seq and small RNA-seq experiments and reconstructed the core human pluripotency network (called PluriMLMiNet) consisting of 375 mRNA, 57 lncRNA and 207 miRNAs. Furthermore, we derived networks specific to the naïve and primed states of human pluripotency (called NaiveMLMiNet and PrimedMLMiNet respectively) that revealed a set of molecular markers (RPS6KA1, ZYG11A, ZNF695, ZNF273, and NLRP2 for naive state, and RAB34, TMEM178B, PTPRZ1, USP44, KIF1A and LRRN1 for primed state) which can be used to distinguish the pluripotent state from the non-pluripotent state and also to identify the intra-pluripotency states (i.e., naïve and primed state). The lncRNA DANT1 was found to be a crucial as it formed a bridge between the naive and primed state-specific networks. Analysis of the genes neighbouring DANT1 suggested its possible role as a competing endogenous RNA (ceRNA) for the induction and maintenance of human pluripotency. This was computationally validated by predicting the missing DANT1-miRNA interactions to complete the ceRNA circuit. Here we first report that DANT1 might harbour binding sites for miRNAs hsa-miR-30c-2-3p, hsa-miR-210–3p and hsa-let-7b-5p which may influence pluripotency.</p></div>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":"135 ","pages":"Article 100738"},"PeriodicalIF":2.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135764322","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":"Differentiation of Uc-MSCs into insulin secreting islet-like clusters by trypsin through TGF-beta signaling pathway","authors":"Feirong Huang ,&nbsp;Jiashuang Lai ,&nbsp;Lixia Qian ,&nbsp;Wanjin Hong ,&nbsp;Liang-cheng Li","doi":"10.1016/j.diff.2023.100744","DOIUrl":"10.1016/j.diff.2023.100744","url":null,"abstract":"<div><p>Differentiation of human umbilical cord mesenchymal stem cells (Uc-MSCs) into islet-like clusters which are capable of synthesizing and secreting insulin can potentially serve as donors for islet transplantation in the patient deficiency in islet β cell function both in type 1 or type 2 diabetic patients. Therefore, we developed an easy and higher efficacy approach by trypsinazing the Uc-MSCs and followed culture in differentiation medium to induce of Uc-MSCs differentiation into islet-like clusters, and the potential mechanism that in the early stage of differentiation was also investigated by using RNA-sequencing and bioinformatics. Results show that induction efficacy was reached to 98% and TGF-β signaling pathway may play critical role in the early stage differentiation, it was further confirmed that the retardant effect of differentiation progress either in cell morphology or in islet specific genes expression can be observed upon blocking the activation of TGF-β signaling pathway using specific inhibitor of LY2109761 (TβRI/II kinase inhibitor). Our current study, for the first time, development a protocol for differentiation of Uc-MSCs into islet-like clusters, and revealed the importance of TGF-β signaling pathway in the early stage of differentiation of Uc-MSCs into islet-like clusters. Our study will provide alternative approach for clinical treatment of either type I or type II diabtes mellitus with dysfunctional pancreatic islets.</p></div>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":"135 ","pages":"Article 100744"},"PeriodicalIF":2.9,"publicationDate":"2023-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138717107","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":"3D hepatic organoid production from human pluripotent stem cells","authors":"Zhe-Long Jin ,&nbsp;KangHe Xu ,&nbsp;Jonghun Kim ,&nbsp;Hao Guo ,&nbsp;Xuerui Yao ,&nbsp;Yong-Nan Xu ,&nbsp;Ying-Hua Li ,&nbsp;DongHee Ryu ,&nbsp;Kee-Pyo Kim ,&nbsp;Kwonho Hong ,&nbsp;Yong-June Kim ,&nbsp;Lin Wang ,&nbsp;Qilong Cao ,&nbsp;Kyun-Hwan Kim ,&nbsp;Nam-Hyung Kim ,&nbsp;Dong Wook Han","doi":"10.1016/j.diff.2023.100742","DOIUrl":"10.1016/j.diff.2023.100742","url":null,"abstract":"<div><p><span>Hepatic organoids might provide a golden opportunity for realizing precision medicine in various hepatic diseases. Previously described hepatic organoid protocols from pluripotent stem cells rely on complicated multiple differentiation steps consisting of both 2D and 3D differentiation procedures. Therefore, the spontaneous formation of hepatic organoids from 2D monolayer culture is associated with a low-throughput production, which might hinder the standardization of hepatic organoid production and hamper the translation of this technology to the clinical or industrial setting. Here we describe the stepwise and fully 3D production of hepatic organoids from human pluripotent stem cells. We optimized every differentiation step by screening for optimal concentrations and timing of differentiation signals in each differentiation step. Hepatic organoids are stably expandable without losing their hepatic functionality. Moreover, upon treatment of drugs with known hepatotoxicity, we found hepatic organoids are more sensitive to drug-induced hepatotoxicity compared with 2D hepatocytes differentiated from PSCs, making them highly suitable for </span><em>in vitro</em> toxicity screening of drug candidates. The standardized fully 3D protocol described in the current study for producing functional hepatic organoids might serve as a novel platform for the industrial and clinical translation of hepatic organoid technology.</p></div>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":"135 ","pages":"Article 100742"},"PeriodicalIF":2.9,"publicationDate":"2023-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138573842","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}