Tcf3 governs stem cell features and represses cell fate determination in skin

被引:255
作者
Nguyen, Hoang [1 ]
Rendl, Michael [1 ]
Fuchs, Elaine [1 ]
机构
[1] Rockefeller Univ, Dept Mammalian Cell Biol & Dev, Howard Hughes Med Inst, New York, NY 10021 USA
关键词
D O I
10.1016/j.cell.2006.07.036
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Many stem cells (SCs) respond to Wnt signaling, but whether beta-catenin's DNA binding partners, the Tcfs, play a role in SCs in the absence of Writs, is unknown. In adult skin, quiescent multipotent progenitors express Tcf3 and commit to a hair cell fate in response to Wnt signaling. We find that embryonic skin progenitors also express Tcf3. Using an inducible system in mice, we show that upon Tcf3 reactivation, committed epidermal cells induce genes associated with an undifferentiated, Wnt-inhibited state and Tcf3 promotes a transcriptional program shared by embryonic and postnatal SCs. Further, Tcf3-repressed genes include transcriptional regulators of the epidermal, sebaceous gland and hair follicle differentiation programs, and correspondingly, all three terminal differentiation pathways are suppressed when Tcf3 is induced postnatally. These data suggest that in the absence of Writ signals, Tcf3 may function in skin SCs to maintain an undifferentiated state and, through Wnt signaling, directs these cells along the hair lineage.
引用
收藏
页码:171 / 183
页数:13
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