SOX9

A stem cell transcriptional regulator of secreted niche signaling factors

Meelis Kadaja, Brice E. Keyes, Mingyan Lin, H. Amalia Pasolli, Maria Genander, Lisa Polak, Nicole Stokes, Deyou Zheng, Elaine Fuchs

Research output: Contribution to journalArticle

81 Citations (Scopus)

Abstract

Hair follicles (HFs) undergo cyclical periods of growth, which are fueled by stem cells (SCs) at the base of the resting follicle. HF-SC formation occurs during HF development and requires transcription factor SOX9. Whether and how SOX9 functions in HF-SC maintenance remain unknown. By conditionally targeting Sox9 in adult HF-SCs, we show that SOX9 is essential for maintaining them. SOX9-deficient HF-SCs still transition from quiescence to proliferation and launch the subsequent hair cycle. However, once activated, bulge HF-SCs begin to differentiate into epidermal cells, which naturally lack SOX9. In addition, as HF-SC numbers dwindle, outer root sheath production is not sustained, and HF downgrowth arrests prematurely. Probing the mechanism, we used RNA sequencing (RNA-seq) to identify SOX9-dependent transcriptional changes and chromatin immunoprecipitation (ChIP) and deep sequencing (ChIP-seq) to identify SOX9-bound genes in HF-SCs. Intriguingly, a large cohort of SOX9-sensitive targets encode extracellular factors, most notably enhancers of Activin/pSMAD2 signaling. Moreover, compromising Activin signaling recapitulates SOX9-dependent defects, and Activin partially rescues them. Overall, our findings reveal roles for SOX9 in regulating adult HF-SC maintenance and suppressing epidermal differentiation in the niche. In addition, our studies expose a role for SCs in coordinating their own behavior in part through non-cell-autonomous signaling within the niche.

Original languageEnglish (US)
Pages (from-to)328-341
Number of pages14
JournalGenes and Development
Volume28
Issue number4
DOIs
StatePublished - Feb 15 2014

Fingerprint

Hair Follicle
Stem Cells
Activins
SOX9 Transcription Factor
Maintenance
RNA Sequence Analysis
High-Throughput Nucleotide Sequencing
Chromatin Immunoprecipitation
Cell Count

Keywords

  • Activin
  • Hair follicle
  • Skin
  • SOX9
  • Stem cells

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

Cite this

Kadaja, M., Keyes, B. E., Lin, M., Amalia Pasolli, H., Genander, M., Polak, L., ... Fuchs, E. (2014). SOX9: A stem cell transcriptional regulator of secreted niche signaling factors. Genes and Development, 28(4), 328-341. https://doi.org/10.1101/gad.233247.113

SOX9 : A stem cell transcriptional regulator of secreted niche signaling factors. / Kadaja, Meelis; Keyes, Brice E.; Lin, Mingyan; Amalia Pasolli, H.; Genander, Maria; Polak, Lisa; Stokes, Nicole; Zheng, Deyou; Fuchs, Elaine.

In: Genes and Development, Vol. 28, No. 4, 15.02.2014, p. 328-341.

Research output: Contribution to journalArticle

Kadaja, M, Keyes, BE, Lin, M, Amalia Pasolli, H, Genander, M, Polak, L, Stokes, N, Zheng, D & Fuchs, E 2014, 'SOX9: A stem cell transcriptional regulator of secreted niche signaling factors', Genes and Development, vol. 28, no. 4, pp. 328-341. https://doi.org/10.1101/gad.233247.113
Kadaja M, Keyes BE, Lin M, Amalia Pasolli H, Genander M, Polak L et al. SOX9: A stem cell transcriptional regulator of secreted niche signaling factors. Genes and Development. 2014 Feb 15;28(4):328-341. https://doi.org/10.1101/gad.233247.113
Kadaja, Meelis ; Keyes, Brice E. ; Lin, Mingyan ; Amalia Pasolli, H. ; Genander, Maria ; Polak, Lisa ; Stokes, Nicole ; Zheng, Deyou ; Fuchs, Elaine. / SOX9 : A stem cell transcriptional regulator of secreted niche signaling factors. In: Genes and Development. 2014 ; Vol. 28, No. 4. pp. 328-341.
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