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

Hoang Nguyen1, Michael Rendl, Elaine Fuchs

  • 1Howard Hughes Medical Institute, Department of Mammalian Cell Biology and Development, The Rockefeller University, 1230 York Avenue, Box 300, New York, NY 10021, USA.

Cell
|October 5, 2006
PubMed

Insights

Tcf3, a DNA-binding partner of beta-catenin, maintains skin stem cells (SCs) in an undifferentiated state without Wnt signals. Upon Wnt activation, Tcf3 directs SCs toward hair cell fate.

Area of Science:

  • Developmental Biology
  • Stem Cell Biology
  • Dermatology

Background:

  • Stem cells (SCs) often rely on Wnt signaling for differentiation.
  • The role of Tcf3, a beta-catenin DNA-binding partner, in SCs without Wnt signaling is unclear.
  • Skin progenitors express Tcf3 and respond to Wnt signaling for hair cell fate.

Purpose of the Study:

  • To investigate the function of Tcf3 in skin stem cells in the absence of Wnt signaling.
  • To determine if Tcf3 can maintain stem cell populations and influence differentiation pathways.
  • To elucidate the role of Tcf3 in the transcriptional regulation of skin progenitor cells.

Main Methods:

  • Utilized an inducible system in mice to control Tcf3 expression in skin progenitors.
  • Analyzed gene expression changes upon Tcf3 reactivation in committed epidermal cells.
  • Investigated the impact of Tcf3 induction on epidermal, sebaceous gland, and hair follicle differentiation pathways.

Main Results:

  • Tcf3 reactivation in committed epidermal cells induced genes associated with an undifferentiated, Wnt-inhibited state.
  • Tcf3 promoted a transcriptional program common to embryonic and postnatal skin stem cells.
  • Tcf3 repressed genes involved in epidermal, sebaceous gland, and hair follicle differentiation, suppressing these pathways upon induction.

Conclusions:

  • Tcf3 functions in skin SCs to maintain an undifferentiated state in the absence of Wnt signals.
  • Wnt signaling, in conjunction with Tcf3, directs skin SCs toward hair lineage commitment.
  • Tcf3 plays a critical role in regulating the balance between stem cell self-renewal and differentiation in the skin.

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