TFCP2L1 represses multiple lineage commitment of mouse embryonic stem cells through MTA1 and LEF1
TFCP2L1 represses multiple lineage commitment of mouse embryonic stem cells through MTA1 and LEF1
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TFCP2L1通过MTA1和LEF1抑制小鼠胚胎干细胞的多谱系定向
DOI：
10.1242/jcs.206532
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发表时间：
2017-11-15
影响因子：
4
通讯作者：
Ye, Shoudong
中科院分区：
文献类型：
--
作者：
Liu, Kuisheng;Zhang, Yan;Ye, Shoudong
ABSTRACT TFCP2L1 is a transcription factor that is crucial for self-renewal of mouse embryonic stem cells (mESCs). How TFCP2L1 maintains the pluripotent state of mESCs, however, remains unknown. Here, we show that knockdown of Tfcp2l1 in mESCs induces the expression of endoderm, mesoderm and trophectoderm markers. Functional analysis of mutant forms of TFCP2L1 revealed that TFCP2L1 depends on its N-terminus and CP2-like domain to maintain the undifferentiated state of mESCs. The N-terminus of TFCP2L1 is mainly associated with the suppression of mesoderm and trophectoderm differentiation, while the CP2-like domain is closely related to the suppression of endoderm commitment. Further studies showed that MTA1 directly interacts with TFCP2L1 and is indispensable for the TFCP2L1-mediated self-renewal-promoting effect and endoderm-inhibiting action. TFCP2L1-mediated suppression of mesoderm and trophectoderm differentiation, however, seems to be due to downregulation of Lef1 expression. Our study thus provides an expanded understanding of the function of TFCP2L1 and the pluripotency regulation network of ESCs. Summary: TFCP2L1 interacts with MTA1 to inhibit endoderm specification, while suppressing mesoderm and trophectoderm differentiation, in part, through downregulation of Lef1 expression.
