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Endogenous IGF Signaling Directs Heterogeneous Mesoderm Differentiation in Human Embryonic Stem Cells
Yang,Yang1; Ren,Zhili1; Xu,Faxiang1; Meng,Ya1; Zhang,Yumeng1; Ai,Nana1; Long,Yan1,2; Fok,Hio Ian1,3; Deng,Chunhao1; Zhao,Xianyang4; Huang,Liancheng5; Zhao,Qi1; Wang,Jiaxian6; Liu,Weiwei1,3; Ge,Wei1; Chen,Guokai1
2019-12-10
Source PublicationCell Reports
Volume29Issue:11Pages:3374-3384.e5
Abstract

During embryogenesis, various cell types emerge simultaneously from their common progenitors under the influence of intrinsic signals. Human embryonic stem cells can differentiate to diverse cell types of three embryonic lineages, making them an excellent system for understanding the regulatory mechanism that maintains the balance of different cell types in embryogenesis. In this report, we demonstrate that insulin-like growth factor (IGF) proteins are endogenously expressed during differentiation, and their temporal expression contributes to the cell fate diversity in mesoderm differentiation. Small molecule LY294002 inhibits the IGF pathway to promote cardiomyocyte differentiation while suppressing epicardial and noncardiac cell fates. LY294002-induced cardiomyocytes demonstrate characteristic cardiomyocyte features and provide insights into the molecular mechanisms underlying cardiac differentiation. We further show that LY294002 induces cardiomyocytes through CK2 pathway inhibition. This study elucidates the crucial roles of endogenous IGF in mesoderm differentiation and shows that the inhibition of the IGF pathway is an effective approach for generating cardiomyocytes. Yang et al. demonstrate that temporal regulation by insulin/IGF is essential for cell-type heterogeneity during human embryonic stem cell (hESC) differentiation. Inhibition of the endogenous IGF pathway promotes cardiomyocyte differentiation from mesoderm progenitors.

KeywordCardiomyocyte Casein Kinase Ii Heterogeneity Human Embryonic Stem Cells Igf Insulin Mesoderm Pi3k Temporal Regulation Wnt
DOI10.1016/j.celrep.2019.11.047
URLView the original
Indexed BySCIE
Language英語English
WOS Research AreaCell Biology
WOS SubjectCell Biology
WOS IDWOS:000502113400004
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Cited Times [WOS]:2   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionFaculty of Health Sciences
Corresponding AuthorChen,Guokai
Affiliation1.Centre of Reproduction,Development and Aging,Faculty of Health Sciences,University of Macau,Taipa,Macao
2.Department of Cardiac Surgery,The First Affiliated Hospital of Sun Yat-sen University,Guangzhou,China
3.Bioimaging and Stem Cell Core Facility,Faculty of Health Sciences,University of Macau,Taipa,
4.HELP Stem Cell Innovations Ltd. Co.,Nanjing,China
5.Guangzhou FulenGen Co.,Ltd.,Guangzhou,China
6.Department of Cardiology,the First Affiliated Hospital of Nanjing Medical University,Nanjing,China
First Author AffilicationFaculty of Health Sciences
Corresponding Author AffilicationFaculty of Health Sciences
Recommended Citation
GB/T 7714
Yang,Yang,Ren,Zhili,Xu,Faxiang,et al. Endogenous IGF Signaling Directs Heterogeneous Mesoderm Differentiation in Human Embryonic Stem Cells[J]. Cell Reports,2019,29(11):3374-3384.e5.
APA Yang,Yang.,Ren,Zhili.,Xu,Faxiang.,Meng,Ya.,Zhang,Yumeng.,...&Chen,Guokai.(2019).Endogenous IGF Signaling Directs Heterogeneous Mesoderm Differentiation in Human Embryonic Stem Cells.Cell Reports,29(11),3374-3384.e5.
MLA Yang,Yang,et al."Endogenous IGF Signaling Directs Heterogeneous Mesoderm Differentiation in Human Embryonic Stem Cells".Cell Reports 29.11(2019):3374-3384.e5.
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