Mechanisms of Development最新文献_第3页

The transcription factor scleraxis differentially regulates gene expression in tenocytes isolated at different developmental stages 转录因子scleraxis在不同发育阶段分离的细胞中调控基因表达的差异

IF 2.6

Mechanisms of Development Pub Date : 2020-09-01 DOI: 10.1016/j.mod.2020.103635

Y.Z. Paterson , N. Evans , S. Kan , A. Cribbs , F.M.D. Henson , D.J. Guest

{"title":"The transcription factor scleraxis differentially regulates gene expression in tenocytes isolated at different developmental stages","authors":"Y.Z. Paterson , N. Evans , S. Kan , A. Cribbs , F.M.D. Henson , D.J. Guest","doi":"10.1016/j.mod.2020.103635","DOIUrl":"10.1016/j.mod.2020.103635","url":null,"abstract":"<div><p>The transcription factor scleraxis (SCX) is expressed throughout tendon development and plays a key role in directing tendon wound healing. However, little is known regarding its role in fetal or young postnatal tendons, stages in development that are known for their enhanced regenerative capabilities. Here we used RNA-sequencing to compare the transcriptome of adult and fetal tenocytes following SCX knockdown. SCX knockdown had a larger effect on gene expression in fetal tenocytes, affecting 477 genes in comparison to the 183 genes affected in adult tenocytes, indicating that scleraxis-dependent processes may differ in these two developmental stages. Gene ontology, network and pathway analysis revealed an overrepresentation of extracellular matrix (ECM) remodelling processes within both comparisons. These included several matrix metalloproteinases, proteoglycans and collagens, some of which were also investigated in SCX knockdown tenocytes from young postnatal foals. Using chromatin immunoprecipitation, we also identified novel genes that SCX differentially interacts with in adult and fetal tenocytes. These results indicate a role for SCX in modulating ECM synthesis and breakdown and provide a useful dataset for further study into SCX gene regulation.</p></div>","PeriodicalId":49844,"journal":{"name":"Mechanisms of Development","volume":"163 ","pages":"Article 103635"},"PeriodicalIF":2.6,"publicationDate":"2020-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.mod.2020.103635","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38265255","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 5

Regulation of axial and head patterning during planarian regeneration by a commensal bacterium 一种共生细菌对涡虫再生过程中轴头形态的调控

IF 2.6

Mechanisms of Development Pub Date : 2020-09-01 DOI: 10.1016/j.mod.2020.103614

Katherine B. Williams, Johanna Bischof, Frederick J. Lee, Kelsie A. Miller, Jennifer V. LaPalme, Benjamin E. Wolfe, Michael Levin

{"title":"Regulation of axial and head patterning during planarian regeneration by a commensal bacterium","authors":"Katherine B. Williams, Johanna Bischof, Frederick J. Lee, Kelsie A. Miller, Jennifer V. LaPalme, Benjamin E. Wolfe, Michael Levin","doi":"10.1016/j.mod.2020.103614","DOIUrl":"10.1016/j.mod.2020.103614","url":null,"abstract":"<div><p>Some animals, such as planaria, can regenerate complex anatomical structures in a process regulated by genetic and biophysical factors, but additional external inputs into regeneration remain to be uncovered. Microbial communities inhabiting metazoan organisms are important for metabolic, immune, and disease processes, but their instructive influence over host structures remains largely unexplored. Here, we show that <em>Aquitalea</em> sp. FJL05, an endogenous commensal bacterium of <em>Dugesia japonica</em> planarians, and one of the small molecules it produces, indole, can influence axial and head patterning during regeneration, leading to regeneration of permanently two-headed animals. Testing the impact of indole on planaria tissues via RNA sequencing, we find that indole alters the regenerative outcomes in planarians through changes in expression to patterning genes, including a downregulation of Wnt pathway genes. These data provide a unique example of the product of a commensal bacterium modulating transcription of patterning genes to affect the host's anatomical structure during regeneration.</p></div>","PeriodicalId":49844,"journal":{"name":"Mechanisms of Development","volume":"163 ","pages":"Article 103614"},"PeriodicalIF":2.6,"publicationDate":"2020-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.mod.2020.103614","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37961539","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 20

CFTR deficiency causes cardiac dysplasia during zebrafish embryogenesis and is associated with dilated cardiomyopathy CFTR缺乏导致斑马鱼胚胎发育过程中的心脏发育不良，并与扩张型心肌病有关

IF 2.6

Mechanisms of Development Pub Date : 2020-09-01 DOI: 10.1016/j.mod.2020.103627

Yanyan Liu , Ziyuan Lin , Mingfeng Liu , Huijuan Liao , Yan Chen , Xiaohu Zhang , Hsiao Chang Chan , Bin Zhou , Li Rao , Huaqin Sun

{"title":"CFTR deficiency causes cardiac dysplasia during zebrafish embryogenesis and is associated with dilated cardiomyopathy","authors":"Yanyan Liu , Ziyuan Lin , Mingfeng Liu , Huijuan Liao , Yan Chen , Xiaohu Zhang , Hsiao Chang Chan , Bin Zhou , Li Rao , Huaqin Sun","doi":"10.1016/j.mod.2020.103627","DOIUrl":"10.1016/j.mod.2020.103627","url":null,"abstract":"<div><p>Mutations in the <em>CFTR</em> gene cause cystic fibrosis (CF) with myocardial dysfunction. However, it remains unknown whether CF-related heart disease is a secondary effect of pulmonary disease, or an intrinsic primary defect in the heart. Here, we used zebrafish, which lack lung tissue, to investigate the role of CFTR in cardiogenesis. Our findings demonstrated that the loss of CFTR impairs cardiac development from the cardiac progenitor stage, resulting in cardiac looping defects, a dilated atrium, pericardial edema, and a decrease in heart rate. Furthermore, we found that cardiac development was perturbed in wild-type embryos treated with a gating-specific CFTR channel inhibitor, CFTRinh-172, at the blastula stage of development, but not at later stages. Gene expression analysis of blastulas indicated that transcript levels, including mRNAs associated with cardiovascular diseases, were significantly altered in embryos derived from <em>cftr</em> mutants relative to controls. To evaluate the role of CFTR in human heart failure, we performed a genetic association study on individuals with dilated cardiomyopathy and found that the I556V mutation in CFTR, which causes a channel defect, was associated with the disease. Similar to other well-studied channel-defective CFTR mutants, <em>CFTR</em> I556V mRNA failed to restore cardiac dysplasia in mutant embryos. The present study revealed an important role for the CFTR ion channel in regulating cardiac development during early embryogenesis, supporting the hypothesis that CF-related heart disease results from an intrinsic primary defect in the heart.</p></div>","PeriodicalId":49844,"journal":{"name":"Mechanisms of Development","volume":"163 ","pages":"Article 103627"},"PeriodicalIF":2.6,"publicationDate":"2020-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.mod.2020.103627","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38075188","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Brachyury in the gastrula of basal vertebrates 基生脊椎动物原肠中的腕足

IF 2.6

Mechanisms of Development Pub Date : 2020-09-01 DOI: 10.1016/j.mod.2020.103625

Ashley E.E. Bruce, Rudolf Winklbauer

{"title":"Brachyury in the gastrula of basal vertebrates","authors":"Ashley E.E. Bruce, Rudolf Winklbauer","doi":"10.1016/j.mod.2020.103625","DOIUrl":"10.1016/j.mod.2020.103625","url":null,"abstract":"<div><p>The Brachyury gene encodes a transcription factor that is conserved across all animals. In non-chordate metazoans, brachyury is primarily expressed in ectoderm regions that are added to the endodermal gut during development, and often form a ring around the site of endoderm internalization in the gastrula, the blastopore. In chordates, this brachyury ring is conserved, but the gene has taken on a new role in the formation of the mesoderm. In this phylum, a novel type of mesoderm that develops into notochord and somites has been added to the ancestral lateral plate mesoderm. Brachyury contributes to a shift in cell fate from neural ectoderm to posterior notochord and somites during a major lineage segregation event that in Xenopus and in the zebrafish takes place in the early gastrula. In the absence of this brachyury function, impaired formation of posterior mesoderm indirectly affects the gastrulation movements of peak involution and convergent extension. These movements are confined to specific regions and stages, leaving open the question why brachyury expression in an extensive, coherent ring, before, during and after gastrulation, is conserved in the two species whose gastrulation modes differ considerably, and also in many other metazoan gastrulae of diverse structure.</p></div>","PeriodicalId":49844,"journal":{"name":"Mechanisms of Development","volume":"163 ","pages":"Article 103625"},"PeriodicalIF":2.6,"publicationDate":"2020-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.mod.2020.103625","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38036145","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 12

Second heart field-specific expression of Nkx2-5 requires promoter proximal interaction with Srf Nkx2-5的第二心脏区特异性表达需要启动子近端与Srf相互作用

IF 2.6

Mechanisms of Development Pub Date : 2020-06-01 DOI: 10.1016/j.mod.2020.103615

Christopher D. Clark , Kyu-Ho Lee

引用次数: 4

Rb family-independent activating E2F increases genome stability, promotes homologous recombination, and decreases non-homologous end joining Rb家族独立激活E2F增加了基因组的稳定性，促进了同源重组，减少了非同源末端连接

IF 2.6

Mechanisms of Development Pub Date : 2020-06-01 DOI: 10.1016/j.mod.2020.103607

Xun Pei , Elbert Du , Zhentao Sheng , Wei Du

{"title":"Rb family-independent activating E2F increases genome stability, promotes homologous recombination, and decreases non-homologous end joining","authors":"Xun Pei , Elbert Du , Zhentao Sheng , Wei Du","doi":"10.1016/j.mod.2020.103607","DOIUrl":"10.1016/j.mod.2020.103607","url":null,"abstract":"<div><p>The retinoblastoma protein Rb is a prototype tumor suppressor inactivated in a variety of cancers. In addition to deregulated cell proliferation, Rb inactivation also causes genome instability that contributes to tumorigenesis. Although the genome instability effects of Rb inactivation was shown to be mediated mainly by E2F-independent mechanisms, little is known about whether the constitutive free activating E2F proteins released by Rb-inactivation affects genome stability. In this manuscript, we take advantage of the <em>dE2F1</em><sup><em>su89</em></sup> mutant, which contains a point mutation in the conserved Rb-binding domain that disrupts its interaction with the Rb family proteins, to characterize the effect of constitutive free activating E2F on genome stability in the presence of WT Rb. We showed that <em>dE2F1</em><sup><em>su89</em></sup> promoted genome stability in the <em>mwh</em> genome stability assay. We found that the genome stability effects of <em>dE2F1</em><sup><em>su89</em></sup> was sensitive to the levels of activating E2F activity and to the levels of E2F targets involved in DNA replication and repair but not to the level of E2F cell cycle target Cyclin E. Importantly, we showed that <em>dE2F1</em><sup><em>su89</em></sup> promoted DNA double-strand break (DSB) repair by homologous recombination and decreased DSB repair by Non-homologous end joining (NHEJ). These results show that the constitutive free activating E2F promotes genome stability, which potentially contributes the observed tumor development in E2F1 knockout mice and the reported NHEJ defects in Rb mutant cells. These results also explain why constitutive free activating E2F alone was not sufficient for tumor development.</p></div>","PeriodicalId":49844,"journal":{"name":"Mechanisms of Development","volume":"162 ","pages":"Article 103607"},"PeriodicalIF":2.6,"publicationDate":"2020-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.mod.2020.103607","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37776301","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 3

Postnatal development in the rat: Changes in Na+ flux, sodium pump molecular activity and membrane lipid composition 大鼠出生后发育:Na+通量、钠泵分子活性和膜脂组成的变化

IF 2.6

Mechanisms of Development Pub Date : 2020-06-01 DOI: 10.1016/j.mod.2020.103610

Paul L. Else

{"title":"Postnatal development in the rat: Changes in Na+ flux, sodium pump molecular activity and membrane lipid composition","authors":"Paul L. Else","doi":"10.1016/j.mod.2020.103610","DOIUrl":"10.1016/j.mod.2020.103610","url":null,"abstract":"<div><p>The cellular mechanisms underpinning changes in metabolism during postnatal development in young mammals have not been extensively examined. This study examines changes in sodium pump capacity (Na<sup>+</sup>, K<sup>+</sup>-ATPase activity), number and molecular activity, as well as, Na<sup>+</sup> flux, cholesterol level and fatty acid composition in a number of major organs during postnatal development in the rat. In liver, Na<sup>+</sup> flux was highest (2.6 times) in the youngest rats (3-day old) and decreased with increasing age, whereas Na<sup>+</sup>, K<sup>+</sup>-ATPase activity increased with age (up to 9–28 days) in liver, kidney and brain, but not in heart. Increases in Na<sup>+</sup>, K<sup>+</sup>-ATPase activity where primarily driven by increases in molecular activity, 4-fold in brain and 7-fold in kidney, rather than by increases in sodium pump number. Membrane polyunsaturation increased in both kidney and brain during development, with kidney becoming increasingly dominated by omega-6 (18:2n-6 and 20:4n-6) and brain by omega-3 (22:6n-3) fatty acids. Membrane reconstitution experiments support the concept that changes in membrane composition might underpin higher sodium molecular activities in the adult. In conclusion, at birth rats possess high Na<sup>+</sup> flux but a lower sodium pump capacity that increases with age being driven by increases in molecular activities associate with changes in membrane lipid composition.</p></div>","PeriodicalId":49844,"journal":{"name":"Mechanisms of Development","volume":"162 ","pages":"Article 103610"},"PeriodicalIF":2.6,"publicationDate":"2020-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.mod.2020.103610","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37918746","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 2

HYDIN loss-of-function inhibits GATA4 expression and enhances atrial septal defect risk HYDIN功能丧失抑制GATA4表达，增加房间隔缺损风险

IF 2.6

Mechanisms of Development Pub Date : 2020-06-01 DOI: 10.1016/j.mod.2020.103611

Yu Cao , Junying Guo , Jinping Zhang , Li Li , Hui Wang , Wenjun Ren , Lihong Jiang

{"title":"HYDIN loss-of-function inhibits GATA4 expression and enhances atrial septal defect risk","authors":"Yu Cao , Junying Guo , Jinping Zhang , Li Li , Hui Wang , Wenjun Ren , Lihong Jiang","doi":"10.1016/j.mod.2020.103611","DOIUrl":"10.1016/j.mod.2020.103611","url":null,"abstract":"<div><h3>Background</h3><p>Mutations affecting cardiac structural genes can lead to congenital heart diseases (CHDs). Axonemal Central Pair Apparatus Protein (HYDIN<em>)</em> is a ciliary protein previously linked to congenital cardiomyopathy. However, the role of HYDIN in the aetiology of CHDs is thus far unknown. Herein, we explore the function of HYDIN in heart development and CHDs.</p></div><div><h3>Methods</h3><p>The function of HYDIN in cardiac differentiation was assessed in vitro using HYDIN siRNAs, HYDIN overexpression, and HYDIN short hairpin RNA (shRNA)-GATA binding protein 4 (GATA4) cDNA rescue constructs in the human embryonic stem cell (hESC) line HES3. To assess Hydin's function in vivo, we generated shRNA-mediated Hydin knockdown transgenic mice. We characterized the functional mechanisms of the most common human <em>HYDIN</em> variant associated with atrial septal defect (ASD) risk (71098693 mutant, c.A2207C) in cardiac-differentiating HES3 cells.</p></div><div><h3>Results</h3><p>HYDIN functions as a positive regulator of human cardiomyocyte differentiation and promotes expression of cardiac contractile genes in hESC cells. This is mediated through GATA4, a critical transcription factor in heart development. Cardiac-specific Hydin knockdown in vivo leads to Gata4 downregulation and enhanced atrial septal defect (ASD) risk in mice. The c.A2207C <em>HYDIN</em> mutation reduces GATA4 expression in hESC cells.</p></div><div><h3>Conclusion</h3><p>HYDIN loss-of-function inhibits GATA4 expression and enhances ASD risk. We also establish the regulation of a key transcription factor in heart development by a ciliary protein.</p></div>","PeriodicalId":49844,"journal":{"name":"Mechanisms of Development","volume":"162 ","pages":"Article 103611"},"PeriodicalIF":2.6,"publicationDate":"2020-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.mod.2020.103611","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37908540","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 2

A LCMS-based untargeted lipidomics analysis of cleft palate in mouse 基于lcms的小鼠腭裂非靶向脂质组学分析

IF 2.6

Mechanisms of Development Pub Date : 2020-06-01 DOI: 10.1016/j.mod.2020.103609

Wancong Zhang , Hanxing Zhao , Jiasheng Chen , Xiaoping Zhong , Weiping Zeng , Bingna Zhang , Kai Qi , Zhonglei Li , Jianda Zhou , Lungang Shi , Zhihao He , Shijie Tang

{"title":"A LCMS-based untargeted lipidomics analysis of cleft palate in mouse","authors":"Wancong Zhang , Hanxing Zhao , Jiasheng Chen , Xiaoping Zhong , Weiping Zeng , Bingna Zhang , Kai Qi , Zhonglei Li , Jianda Zhou , Lungang Shi , Zhihao He , Shijie Tang","doi":"10.1016/j.mod.2020.103609","DOIUrl":"10.1016/j.mod.2020.103609","url":null,"abstract":"<div><h3>Background</h3><p>Recent studies have shown that lipid metabolism was abnormal during the formation of cleft palate. However, the composition of these lipid species remains unclear.</p></div><div><h3>Objective</h3><p>Aims of this study were to identify the lipid species components and reveal the key lipid metabolic disorders in cleft palate formation.</p></div><div><h3>Methods</h3><p>The pregnant mice were divided into experimental group exposed to all-trans retinoic acid (RA-treated group) (n = 12) and control group (n = 12) at embryonic gestation day 10.5 (E0.5). The component of the palatal tissue metabolome was analyzed using a LCMS-based nontargeted lipidomics approach. Multivariate statistical analysis was then carried out to assess the differences between the RA-treated group and the control group.</p></div><div><h3>Results</h3><p>Twenty-nine lipid species were found to discriminate between RA-treated and control embryos. Among them, 28 lipid species increased and 1 lipid species decreased in the RA-treated group. Among these lipids, 13 were triglycerides, 9 were PEs, 3 were PCs, 2 were PSs, 2 were DGs. Further analysis of the number of carbons and unsaturated bond of triglycerides showed that TGs with high unsaturated bonds constituted a higher fraction in the RA-treated group. A higher amount of triglycerides containing 52, 54, 56, 58, 60 carbons, and 1 to 8 unsaturated bonds. Of note, under RA treatment, TG 50:1, 52:2, 56:6and 60:8 became the most prominent.</p></div><div><h3>Conclusion</h3><p>Lipid metabolism is significantly different in the formation of cleft palate induced by RA, and the unsaturated triglycerides increased in the RA-treated group may play an important role in the formation of cleft palate.</p></div>","PeriodicalId":49844,"journal":{"name":"Mechanisms of Development","volume":"162 ","pages":"Article 103609"},"PeriodicalIF":2.6,"publicationDate":"2020-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.mod.2020.103609","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37936213","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 4

Long noncoding RNA XIST regulates osteogenic differentiation of human bone marrow mesenchymal stem cells by targeting miR-9-5p 长链非编码RNA XIST通过靶向miR-9-5p调控人骨髓间充质干细胞成骨分化

IF 2.6

Mechanisms of Development Pub Date : 2020-06-01 DOI: 10.1016/j.mod.2020.103612

Chenying Zheng, Chunxiao Bai, Qi Sun, Fan Zhang, Qinsheng Yu, Xueqian Zhao, Shengqian Kang, Jinyu Li, Yusong Jia

{"title":"Long noncoding RNA XIST regulates osteogenic differentiation of human bone marrow mesenchymal stem cells by targeting miR-9-5p","authors":"Chenying Zheng, Chunxiao Bai, Qi Sun, Fan Zhang, Qinsheng Yu, Xueqian Zhao, Shengqian Kang, Jinyu Li, Yusong Jia","doi":"10.1016/j.mod.2020.103612","DOIUrl":"10.1016/j.mod.2020.103612","url":null,"abstract":"<div><p>This study aimed to investigate whether X inactivate-specific transcript (XIST) regulated the expression of tissue non-specific alkaline phosphatase (ALPL) through miR-9-5p to promote osteogenic differentiation of human bone marrow-derived mesenchymal stem cells (hBMSCs). We elucidated the molecular regulation mechanisms of XIST underlying osteogenic differentiation of hBMSCs. In osteoporotic patients with hBMSCs, the expression of miR-9-5p was upregulated and the expression of XIST was downregulated. When hBMSCs were treated with osteogenic induction, the expression of XIST was increased and the expression of miR-9-5p was decreased. The osteogenic differentiation of hBMSCs was significantly decreased after knocking down XIST. Luciferase analysis revealed that XIST could directly bind to miR-9-5p and exert a negative regulatory effect on its expression. MiR-9-5p could bind directly to the 3′-UTR of ALPL and inhibit the expression of ALPL. Knockout of XIST reduced the expression of ALPL, while co-transfection of the miR-9-5p inhibitor could reverse the expression of the ALPL gene. In hBMSCs, overexpression of XIST upregulated the expression of ALPL, but the miR-9-5p mimic could reverse the expression of ALPL. Furthermore, silencing of ALPL could downregulate the expression of osteopontin(OPN) and osteocalcin(OCN) induced by miR-9-5p inhibitors. In conclusion, XIST regulated the expression of ALPL by targeting miR-9-5p. It could be used as a positive regulator of osteogenic differentiation of hBMSC.</p></div>","PeriodicalId":49844,"journal":{"name":"Mechanisms of Development","volume":"162 ","pages":"Article 103612"},"PeriodicalIF":2.6,"publicationDate":"2020-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.mod.2020.103612","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37920225","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 20