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Constitutive Stat3 activation alters behavior of hair follicle stem and progenitor cell populations

Dharanija Rao1, Everardo Macias, Steve Carbajal

  • 1Division of Pharmacology and Toxicology, College of Pharmacy, The University of Texas at Austin, Austin, Texas; Department of Molecular Carcinogenesis, UT MD Anderson Cancer Center, Graduate School of Biomedical Sciences, Smithville, Texas.

Molecular Carcinogenesis
|September 17, 2013
PubMed

Insights

Constitutively active Signal Transducer and Activator of Transcription 3 (STAT3) significantly alters keratinocyte stem cell populations in mice. Elevated STAT3 activity depletes hair follicle stem cells while increasing other progenitor cells, impacting skin homeostasis.

Area of Science:

  • Dermatology
  • Molecular Biology
  • Stem Cell Biology

Background:

  • Signal Transducer and Activator of Transcription (STAT) proteins are critical for numerous biological processes.
  • STAT3 is implicated in cell development, proliferation, differentiation, migration, and cancer.
  • Understanding STAT3's role in keratinocyte stem cells (KSCs) is vital for skin biology and disease.

Purpose of the Study:

  • To investigate the in vivo effects of constitutive STAT3 activation on keratinocyte behavior.
  • To analyze the impact on hair follicle KSCs and other stem/progenitor cell populations.

Main Methods:

  • Utilized BK5.Stat3C transgenic (Tg) mice expressing a constitutively active form of STAT3 (STAT3C).
  • Compared KSC populations (CD34+/α6 integrin+) in Tg mice versus non-transgenic (NTg) littermates.
  • Analyzed gene expression of stem cell markers (Lgr-6, Lrig-1, Sca-1), c-myc, β-catenin, and EMT-related genes.

Main Results:

  • Tg mice showed a significant reduction in CD34+/α6 integrin+ KSCs.
  • Increased populations of Lgr-6, Lrig-1, and Sca-1 cells were observed in Tg mice.
  • Elevated c-myc, β-catenin, and EMT genes, with decreased α6-integrin expression in hair follicles of Tg mice.
  • Sca-1 was identified as a direct transcriptional target of STAT3 in keratinocytes.

Conclusions:

  • Constitutive STAT3 activation leads to the depletion of hair follicle KSCs.
  • STAT3C expression results in an increase of stem/progenitor cells residing above the bulge region.
  • STAT3 plays a crucial role in maintaining keratinocyte stem/progenitor cell homeostasis.
Keywords:
Sca-1Stat3Cbulge regionkeratinocyte stem cellsskin carcinogenesis

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