PUBLICATION
Endogenous IGF Signaling Directs Heterogeneous Mesoderm Differentiation in Human Embryonic Stem Cells
- Authors
- Yang, Y., Ren, Z., Xu, F., Meng, Y., Zhang, Y., Ai, N., Long, Y., Fok, H.I., Deng, C., Zhao, X., Huang, L., Zhao, Q., Wang, J., Liu, W., Ge, W., Chen, G.
- ID
- ZDB-PUB-230503-59
- Date
- 2019
- Source
- Cell Reports 29: 33743384.e53374-3384.e5 (Journal)
- Registered Authors
- Keywords
- IGF, PI3K, WNT, cardiomyocyte, casein kinase II, heterogeneity, human embryonic stem cells, insulin, mesoderm, temporal regulation
- MeSH Terms
-
- Casein Kinase II/antagonists & inhibitors
- Casein Kinase II/metabolism
- Cell Differentiation*
- Cells, Cultured
- Chromones/pharmacology
- Human Embryonic Stem Cells/cytology*
- Human Embryonic Stem Cells/drug effects
- Human Embryonic Stem Cells/metabolism
- Humans
- Mesoderm/cytology
- Mesoderm/metabolism
- Morpholines/pharmacology
- Myocytes, Cardiac/cytology
- Myocytes, Cardiac/metabolism
- Protein Kinase Inhibitors/pharmacology
- Signal Transduction*
- Somatomedins/metabolism*
- PubMed
- 31825822 Full text @ Cell Rep.
Citation
Yang, Y., Ren, Z., Xu, F., Meng, Y., Zhang, Y., Ai, N., Long, Y., Fok, H.I., Deng, C., Zhao, X., Huang, L., Zhao, Q., Wang, J., Liu, W., Ge, W., Chen, G. (2019) Endogenous IGF Signaling Directs Heterogeneous Mesoderm Differentiation in Human Embryonic Stem Cells. Cell Reports. 29:33743384.e53374-3384.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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping