Stem cells repurpose proliferation to contain a breach in their niche barrier
- Howard Hughes Medical Institute, The Rockefeller University, United States
- Janelia Research Campus, Howard Hughes Medical Institute, United States
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.
Reviewing Editor
- Valerie Horsley, Yale University, United States
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.
Version 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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Stem cells repurpose proliferation to contain a breach in their niche barrier
eLife 7:e41661.
https://doi.org/10.7554/eLife.41661
Further reading
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- Developmental Biology
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Endothelial and skeletal muscle lineages arise from common embryonic progenitors. Despite their shared developmental origin, adult endothelial cells (ECs) and muscle stem cells (MuSCs; satellite cells) have been thought to possess distinct gene signatures and signaling pathways. Here, we shift this paradigm by uncovering how adult MuSC behavior is affected by the expression of a subset of EC transcripts. We used several computational analyses including single-cell RNA-seq (scRNA-seq) to show that MuSCs express low levels of canonical EC markers in mice. We demonstrate that MuSC survival is regulated by one such prototypic endothelial signaling pathway (VEGFA-FLT1). Using pharmacological and genetic gain- and loss-of-function studies, we identify the FLT1-AKT1 axis as the key effector underlying VEGFA-mediated regulation of MuSC survival. All together, our data support that the VEGFA-FLT1-AKT1 pathway promotes MuSC survival during muscle regeneration, and highlights how the minor expression of select transcripts is sufficient for affecting cell behavior.
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