IP3R-mediated Ca2+ signals govern hematopoietic and cardiac divergence of Flk1(+) cells via the calcineurin-NFATc3-Etv2 pathway
文献类型:期刊论文
作者 | Wang, Yi-Jie1,2,3; Huang, Jijun1,2,3; Yu, Xiujian1,2,3; Yang, Huang-Tian1,2,3; Liu, Wenqiang4; Kou, Xiaochen4; Gao, Shaorong4; Tang, Huayuan5; Wang, Hong5; Ouyang, Kunfu5 |
刊名 | JOURNAL OF MOLECULAR CELL BIOLOGY
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出版日期 | 2017 |
卷号 | 9期号:4页码:274-288 |
关键词 | IP(3)Rs Ca2+ signals mesoderm specification hematopoietic and cardiac fate Etv2 |
ISSN号 | 1674-2788 |
DOI | 10.1093/jmcb/mjx014 |
文献子类 | Article |
英文摘要 | Ca2+ signals participate in various cellular processes with spatial and temporal dynamics, among which, inositol 1,4,5-trisphosphate receptors (IP(3)Rs)-mediated Ca2+ signals are essential for early development. However, the underlying mechanisms of IP3R-regulated cell fate decision remain largely unknown. Here we report that IP(3)Rs are required for the hematopoietic and cardiac fate divergence of mouse embryonic stem cells (mESCs). Deletion of IP(3)Rs (IP3R-tKO) reduced Flk1(+)/PDGFR alpha(-) hematopoietic mesoderm, c-Kit(+)/CD41(+) hematopoietic progenitor cell population, and the colony-forming unit activity, but increased cardiac progenitor markers as well as cardiomyocytes. Concomitantly, the expression of a key regulator of hematopoiesis, Etv2, was reduced in IP3R-tKO cells, which could be rescued by the activation of Ca2+ signals and calcineurin or overexpression of constitutively active form of NFATc3. Furthermore, IP3R-tKO impaired specific targeting of Etv2 by NFATc3 via its evolutionarily conserved cis-element in differentiating ESCs. Importantly, the activation of Ca2+-calcineurin-NFAT pathway reversed the phenotype of IP3R-tKO cells. These findings reveal an unrecognized governing role of IP(3)Rs in hematopoietic and cardiac fate commitment via IP(3)Rs-Ca2+-calcineurin-NFATc3-Etv2 pathway. |
学科主题 | Cell Biology |
WOS关键词 | EMBRYONIC STEM-CELLS ; CARDIOVASCULAR PROGENITOR CELLS ; ETV2 GENE-EXPRESSION ; KAPPA-B P50 ; MOUSE ; DIFFERENTIATION ; MESODERM ; SPECIFICATION ; CALCIUM ; INDUCTION |
语种 | 英语 |
WOS记录号 | WOS:000412412300003 |
出版者 | OXFORD UNIV PRESS |
版本 | 出版稿 |
源URL | [http://202.127.25.144/handle/331004/1170] ![]() |
专题 | 中国科学院上海生命科学研究院营养科学研究所 |
作者单位 | 1.Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Hlth Sci, Key Lab Stem Cell Biol, Shanghai 200031, Peoples R China; 2.Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Hlth Sci, Lab Mol Cardiol, Shanghai 200031, Peoples R China; 3.Shanghai Jiao Tong Univ, Sch Med, Shanghai 200031, Peoples R China; 4.Tongji Univ, Sch Life Sci & Technol, Shanghai Matern & Infant Hosp 1, Clin & Translat Res Ctr, Shanghai 200092, Peoples R China; 5.Peking Univ, Shenzhen Grad Sch, Key Lab Chem Genom, Drug Discovery Ctr, Shenzhen 518055, Peoples R China; 6.Zhejiang Univ, Affiliated Hosp 2, Hangzhou 310009, Zhejiang, Peoples R China, |
推荐引用方式 GB/T 7714 | Wang, Yi-Jie,Huang, Jijun,Yu, Xiujian,et al. IP3R-mediated Ca2+ signals govern hematopoietic and cardiac divergence of Flk1(+) cells via the calcineurin-NFATc3-Etv2 pathway[J]. JOURNAL OF MOLECULAR CELL BIOLOGY,2017,9(4):274-288. |
APA | Wang, Yi-Jie.,Huang, Jijun.,Yu, Xiujian.,Yang, Huang-Tian.,Liu, Wenqiang.,...&,.(2017).IP3R-mediated Ca2+ signals govern hematopoietic and cardiac divergence of Flk1(+) cells via the calcineurin-NFATc3-Etv2 pathway.JOURNAL OF MOLECULAR CELL BIOLOGY,9(4),274-288. |
MLA | Wang, Yi-Jie,et al."IP3R-mediated Ca2+ signals govern hematopoietic and cardiac divergence of Flk1(+) cells via the calcineurin-NFATc3-Etv2 pathway".JOURNAL OF MOLECULAR CELL BIOLOGY 9.4(2017):274-288. |
入库方式: OAI收割
来源:上海营养与健康研究所
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