Nfatc1 orchestrates aging in hair follicle stem cells

Brice E. Keyes, Jeremy P. Segal, Evan Heller, Wen Hui Lien, Chiung Ying Chang, Xingyi Guo, Dan S. Oristian, Deyou Zheng, Elaine Fuchs

Research output: Contribution to journalArticle

70 Scopus citations

Abstract

Hair production is fueled by stem cells (SCs), which transition between cyclical bouts of rest and activity. Here, we explore why hair growth wanes with age. We show that aged hair follicle SCs (HFSCs) in mice exhibit enhanced resting and abbreviated growth phases and are delayed in response to tissue-regenerating cues. Aged HFSCs are poor at initiating proliferation and show diminished self-renewing capacity upon extensive use. Only modestly restored by parabiosis, these features are rooted in elevated cell-intrinsic sensitivity and local elevation in bone morphogenic protein (BMP) signaling. Transcriptional profiling presents differences consistent with defects in aged HFSC activation. Notably, BMP-/calcium-regulated, nuclear factor of activated T-cell c1 (NFATc1) in HFSCs becomes recalcitrant to its normal down-regulating cues, and NFATc1 ChIP-sequencing analyses reveal a marked enrichment of NFATc1 target genes within the age-related signature. Moreover, aged HFSCs display more youthful levels of hair regeneration when BMP and/or NFATc1 are inhibited. These results provide unique insights into how skin SCs age.

Original languageEnglish (US)
Pages (from-to)E4950-E4959
JournalProceedings of the National Academy of Sciences of the United States of America
Volume110
Issue number51
DOIs
StatePublished - Dec 17 2013

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Keywords

  • BMP signaling
  • Hair cycle
  • Quiescence

ASJC Scopus subject areas

  • General

Cite this

Keyes, B. E., Segal, J. P., Heller, E., Lien, W. H., Chang, C. Y., Guo, X., Oristian, D. S., Zheng, D., & Fuchs, E. (2013). Nfatc1 orchestrates aging in hair follicle stem cells. Proceedings of the National Academy of Sciences of the United States of America, 110(51), E4950-E4959. https://doi.org/10.1073/pnas.1320301110