Stem cells repurpose proliferation to contain a breach in their niche barrier
Abstract
Adult stem cells are responsible for life-long tissue maintenance. They reside in and interact with specialized tissue microenvironments (niches). Using murine hair follicle as a model, we show that when junctional perturbations in the niche disrupt barrier function, adjacent stem cells dramatically change their transcriptome independent of bacterial invasion and become capable of directly signaling to and recruiting immune cells. Additionally, these stem cells elevate cell cycle transcripts which reduce their quiescence threshold, enabling them to selectively proliferate within this microenvironment of immune distress cues. However, rather than mobilizing to fuel new tissue regeneration, these ectopically proliferative stem cells remain within their niche to contain the breach. Together, our findings expose a potential communication relay system that operates from the niche to the stem cells to the immune system and back. The repurposing of proliferation by these stem cells patch the breached barrier, stoke the immune response and restore niche integrity.
Data availability
RNA-sequencing data have been deposited in GEO under accession number GSE106767
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RNA-seq analysis of hair follicle stem cell transcriptome upon loss of the transcription factor FOXC1NCBI Gene Expression Omnibus, GSE77256.
Article and author information
Author details
Funding
National Institutes of Health
- Elaine Fuchs
L'Oreal USA
- Shruti Naik
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All mice were maintained in a facility approved by The Association for Assessment and Accreditation of Laboratory Animal Care (AAALAC), and procedures were performed with protocols approved by Rockefeller University's institutional animal care and use committee (IACUC) members.
Reviewing Editor
- Valerie Horsley, Yale University, United States
Publication history
- Received: September 2, 2018
- Accepted: November 29, 2018
- Accepted Manuscript published: December 6, 2018 (version 1)
- Version of Record published: January 8, 2019 (version 2)
Copyright
© 2018, Lay et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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