Tcf3 governs stem cell features and represses cell fate determination in skin.
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 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.
Nguyen
Hoang
H
Howard Hughes Medical Institute, Department of Mammalian Cell Biology and Development, The Rockefeller University, 1230 York Avenue, Box 300, New York, NY 10021, USA.
Rendl
Michael
M
Fuchs
Elaine
E
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D002454:Cell Differentiation / Q000502:physiology*; D019070:Cell Lineage; D002478:Cells, Cultured; D004318:Doxycycline / Q000494:pharmacology; D053595:Embryonic Stem Cells / Q000166:cytology / Q000502:physiology*; D000078404:Epidermal Cells; D004817:Epidermis / Q000187:drug effects / Q000196:embryology / Q000502:physiology; D018507:Gene Expression Regulation, Developmental; D018859:Hair Follicle / Q000166:cytology / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D039902:Multipotent Stem Cells / Q000166:cytology / Q000502:physiology*; D020411:Oligonucleotide Array Sequence Analysis; D047492:Peroxisome Proliferator-Activated Receptors / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D051820:TCF Transcription Factors / Q000235:genetics / Q000378:metabolism*; D058125:Transcription Factor 7-Like 1 Protein; D051153:Wnt Proteins / Q000378:metabolism*
D000900:Anti-Bacterial Agents; D047492:Peroxisome Proliferator-Activated Receptors; D051820:TCF Transcription Factors; C544913:Tcf7l1 protein, mouse; D058125:Transcription Factor 7-Like 1 Protein; D051153:Wnt Proteins; D004318:Doxycycline