Wnt Signaling Modulates Routes of Retinoic Acid-Induced Differentiation of Embryonic Stem Cells.

Publisher: Mary Ann Liebert, Inc Country of Publication: United States NLM ID: 101197107 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1557-8534 (Electronic) Linking ISSN: 15473287 NLM ISO Abbreviation: Stem Cells Dev Subsets: MEDLINE

Original Publication: Larchmont, NY : Mary Ann Liebert, Inc., c2004-

Cell Differentiation/*drug effects ; Mouse Embryonic Stem Cells/*drug effects ; Myocytes, Smooth Muscle/*drug effects ; Tretinoin/*pharmacology ; Wnt Signaling Pathway/*drug effects; Actins/genetics ; Actins/metabolism ; Animals ; Calcium-Binding Proteins/genetics ; Calcium-Binding Proteins/metabolism ; Cells, Cultured ; Endoderm/cytology ; Endoderm/growth & development ; Endoderm/metabolism ; Epithelial-Mesenchymal Transition/drug effects ; Epithelial-Mesenchymal Transition/genetics ; Feeder Cells ; Fibroblasts/cytology ; Fibroblasts/drug effects ; Fibroblasts/metabolism ; Gene Expression Regulation ; Heterocyclic Compounds, 3-Ring/pharmacology ; Mesoderm/cytology ; Mesoderm/growth & development ; Mesoderm/metabolism ; Mice ; Microfilament Proteins/genetics ; Microfilament Proteins/metabolism ; Mouse Embryonic Stem Cells/cytology ; Mouse Embryonic Stem Cells/metabolism ; Muscle Proteins/genetics ; Muscle Proteins/metabolism ; Myocytes, Smooth Muscle/cytology ; Myocytes, Smooth Muscle/metabolism ; Nanog Homeobox Protein/genetics ; Nanog Homeobox Protein/metabolism ; Nuclear Proteins/genetics ; Nuclear Proteins/metabolism ; Trans-Activators/genetics ; Trans-Activators/metabolism ; Transcription Factor 7-Like 2 Protein/genetics ; Transcription Factor 7-Like 2 Protein/metabolism ; Wnt Signaling Pathway/genetics ; Calponins

Smooth muscle cells (SMCs) are important cell type for regenerative medicine. Previous studies showed that retinoic acid (RA) induces differentiation of SMCs from monolayer-cultured embryonic stem cells (ESCs) with high efficiency. However, the underlying mechanisms are still poorly defined. Here, we identified Wnt signaling as a primary regulator for RA-induced ESC differentiation. The activation of Wnt signaling inhibited the epithelial-mesenchymal transition during ESC differentiation, leading to inhibition of RA-induced SMC differentiation and promoting differentiation of ESCs toward primitive endoderm (PrE) lineage instead, while the inhibition of Wnt signaling promoted RA-induced SMC differentiation. Loss-of-function studies revealed that 7-like 2 (Tcf7l2) was the key transcription factor that Wnt operate through during RA-induced differentiation. Thus, this study revealed that the Tcf7l2-mediated Wnt signaling is a switch in determining the mesoderm/PrE fates in RA-induced ESC differentiation.

Keywords: Tcf7l2; Wnt signaling pathway; differentiation; embryonic stem cells; epithelial–mesenchymal transition; primitive endoderm; smooth muscle cells

0 (Acta2 protein, mouse)
0 (Actins)
0 (Calcium-Binding Proteins)
0 (Heterocyclic Compounds, 3-Ring)
0 (Microfilament Proteins)
0 (Muscle Proteins)
0 (Nanog Homeobox Protein)
0 (Nanog protein, mouse)
0 (Nuclear Proteins)
0 (Tagln protein, mouse)
0 (Tcf7l2 protein, mouse)
0 (Trans-Activators)
0 (Transcription Factor 7-Like 2 Protein)
0 (XAV939)
0 (myocardin)
5688UTC01R (Tretinoin)

Date Created: 20190725 Date Completed: 20200722 Latest Revision: 20231213

20240105

10.1089/scd.2019.0065

31337269