H2AK119ub dynamics controls hair follicle stem cell quiescence

Insights

Repressive histone marks maintain stem cell quiescence. Loss of H2AK119ub in hair follicle stem cells (HFSCs) causes premature activation and exhaustion, revealing epigenetic control of tissue regeneration.

Area of Science:

  • Epigenetics
  • Stem Cell Biology
  • Dermatology

Background:

  • Stem cell activation involves dismantling quiescence programs and establishing cell cycle promotion.
  • The role of epigenetic regulation in adult tissue regeneration via stem cell states is not fully understood.

Purpose of the Study:

  • To investigate the role of the repressive histone modification H2AK119ub in regulating hair follicle stem cell (HFSC) quiescence and activation.
  • To elucidate the mechanisms by which epigenetic processes control stem cell function during tissue regeneration.

Main Methods:

  • Analysis of dynamic H2AK119ub levels in quiescent and active HFSCs in adult murine skin.
  • Genetic ablation of H2AK119ub in HFSCs to assess its impact on quiescence and stem cell pool.
  • Transcriptional and chromatin studies to identify target genes and regulatory pathways.
  • Investigation of niche signaling, specifically FGF signaling, in maintaining H2AK119ub levels.

Main Results:

  • H2AK119ub is dynamically regulated between quiescent and active HFSCs.
  • Ablation of H2AK119ub leads to impaired HFSC quiescence, premature activation, and eventual exhaustion of the stem cell pool.
  • H2AK119ub directly represses a transcriptional program that promotes proliferation in HFSCs.
  • Inhibitory FGF signaling from niche keratinocytes maintains H2AK119ub in quiescent HFSCs.

Conclusions:

  • The repressive histone mark H2AK119ub is crucial for maintaining HFSC quiescence.
  • Dynamic regulation of H2AK119ub by niche signaling prevents untimely stem cell activation, preserving stem cell function and longevity.
  • Epigenetic control via H2AK119ub is essential for adult tissue regeneration and stem cell maintenance.

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