Journal
STEM CELLS AND DEVELOPMENT
Volume 28, Issue 19, Pages 1334-1345Publisher
MARY ANN LIEBERT, INC
DOI: 10.1089/scd.2019.0065
Keywords
embryonic stem cells; differentiation; Wnt signaling pathway; smooth muscle cells; primitive endoderm; epithelial-mesenchymal transition; Tcf7l2
Funding
- Natural Science Foundation of China [31071201]
- Initiative Design Project of Agricultural Research of Hangzhou [20162012A07]
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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.
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