TY - JOUR
T1 - Tcf3 Governs Stem Cell Features and Represses Cell Fate Determination in Skin
AU - Nguyen, Hoang
AU - Rendl, Michael
AU - Fuchs, Elaine
N1 - Funding Information:
We extend a special thank you to H. Amalia Passoli for conducting the ultrastrucural analyses presented in this paper. For generous gifts of reagents and Abs, we thank Wolfgang Hillen, Pierre Coulombe, and Hans Clevers. We thank the Rockefeller University core facility staff (Fred Quimby, LARC; Alison North, Bioimaging Facility; Agnes Viale, Juan Li, and Hui Zhao, Genomics Core Facility; Memorial Sloan Kettering Cancer Research Center), Fuchs' laboratory staff for technical assistance (Maria Nikolova, Lisa Polak, and Nicole Stokes), and the other members of the Fuchs lab for their genuine scientific curiosity and willingness to share ideas, reagents, and protocols. H.N. is the recipient of an NIH-NIAMS postdoctoral fellowship. E.F. is an investigator of the Howard Hughes Medical Institute. This work was supported in part by a grant R01 AR31737 from the NIH (E.F.).
PY - 2006/10/6
Y1 - 2006/10/6
N2 - Many stem cells (SCs) respond to Wnt signaling, but whether β-catenin's DNA binding partners, the Tcfs, play a role in SCs in the absence of Wnts, 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 Wnt signals, Tcf3 may function in skin SCs to maintain an undifferentiated state and, through Wnt signaling, directs these cells along the hair lineage.
AB - Many stem cells (SCs) respond to Wnt signaling, but whether β-catenin's DNA binding partners, the Tcfs, play a role in SCs in the absence of Wnts, 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 Wnt signals, Tcf3 may function in skin SCs to maintain an undifferentiated state and, through Wnt signaling, directs these cells along the hair lineage.
UR - http://www.scopus.com/inward/record.url?scp=33749065765&partnerID=8YFLogxK
U2 - 10.1016/j.cell.2006.07.036
DO - 10.1016/j.cell.2006.07.036
M3 - Article
C2 - 17018284
AN - SCOPUS:33749065765
SN - 0092-8674
VL - 127
SP - 171
EP - 183
JO - Cell
JF - Cell
IS - 1
ER -