Stem cells repurpose proliferation to contain a breach in their niche barrier

  1. Kenneth Lay
  2. Shaopeng Yuan
  3. Shiri Gur-Cohen
  4. Yuxuan Miao
  5. Tianxiao Han
  6. Shruti Naik
  7. H Amalia Pasolli
  8. Samantha B Larsen
  9. Elaine Fuchs  Is a corresponding author
  1. Howard Hughes Medical Institute, The Rockefeller University, United States
  2. 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

The following data sets were generated
The following previously published data sets were used

Article and author information

Author details

  1. Kenneth Lay

    Robin Chemers Neustein Laboratory of Mammalian Cell Biology and Development, Howard Hughes Medical Institute, The Rockefeller University, New York, United States
    Competing interests
    No competing interests declared.
  2. Shaopeng Yuan

    Robin Chemers Neustein Laboratory of Mammalian Cell Biology and Development, Howard Hughes Medical Institute, The Rockefeller University, New York, United States
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9554-1325
  3. Shiri Gur-Cohen

    Robin Chemers Neustein Laboratory of Mammalian Cell Biology and Development, Howard Hughes Medical Institute, The Rockefeller University, New York, United States
    Competing interests
    No competing interests declared.
  4. Yuxuan Miao

    Robin Chemers Neustein Laboratory of Mammalian Cell Biology and Development, Howard Hughes Medical Institute, The Rockefeller University, New York, United States
    Competing interests
    No competing interests declared.
  5. Tianxiao Han

    Robin Chemers Neustein Laboratory of Mammalian Cell Biology and Development, Howard Hughes Medical Institute, The Rockefeller University, New York, United States
    Competing interests
    No competing interests declared.
  6. Shruti Naik

    Robin Chemers Neustein Laboratory of Mammalian Cell Biology and Development, Howard Hughes Medical Institute, The Rockefeller University, New York, United States
    Competing interests
    No competing interests declared.
  7. H Amalia Pasolli

    Electron Microscopy Shared Resource, Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, United States
    Competing interests
    No competing interests declared.
  8. Samantha B Larsen

    Robin Chemers Neustein Laboratory of Mammalian Cell Biology and Development, Howard Hughes Medical Institute, The Rockefeller University, New York, United States
    Competing interests
    No competing interests declared.
  9. Elaine Fuchs

    Robin Neustein Laboratory of Mammalian Development and Cell Biology, Howard Hughes Medical Institute, The Rockefeller University, New York, United States
    For correspondence
    elaine.fuchs@rockefeller.edu
    Competing interests
    Elaine Fuchs, Reviewing editor, eLife.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0978-5137

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

  1. Valerie Horsley, Yale University, United States

Publication history

  1. Received: September 2, 2018
  2. Accepted: November 29, 2018
  3. Accepted Manuscript published: December 6, 2018 (version 1)
  4. 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.

Metrics

  • 4,505
    Page views
  • 758
    Downloads
  • 25
    Citations

Article citation count generated by polling the highest count across the following sources: Crossref, Scopus, PubMed Central.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Kenneth Lay
  2. Shaopeng Yuan
  3. Shiri Gur-Cohen
  4. Yuxuan Miao
  5. Tianxiao Han
  6. Shruti Naik
  7. H Amalia Pasolli
  8. Samantha B Larsen
  9. Elaine Fuchs
(2018)
Stem cells repurpose proliferation to contain a breach in their niche barrier
eLife 7:e41661.
https://doi.org/10.7554/eLife.41661

Further reading

    1. Neuroscience
    2. Stem Cells and Regenerative Medicine
    Alexis Cooper, Benedikt Berninger
    Insight

    New findings cast doubt on whether suppressing the RNA-binding protein PTBP1 can force astrocytes to become dopaminergic neurons.

    1. Cell Biology
    2. Stem Cells and Regenerative Medicine
    Suhita Ray et al.
    Research Article

    Acute anemia induces rapid expansion of erythroid precursors and accelerated differentiation to replenish erythrocytes. Paracrine signals involving cooperation between SCF/Kit signaling and other signaling inputs are required for the increased erythroid precursor activity in anemia. Our prior work revealed that the Sterile Alpha Motif (SAM) Domain 14 (Samd14) gene increases the regenerative capacity of the erythroid system in a mouse genetic model and promotes stress-dependent Kit signaling. However, the mechanism underlying Samd14's role in stress erythropoiesis is unknown. We identified a protein-protein interaction between Samd14 and the α- and β heterodimers of the F-actin capping protein (CP) complex. Knockdown of the CP β subunit increased erythroid maturation in murine ex vivo cultures and decreased colony forming potential of stress erythroid precursors. In a genetic complementation assay for Samd14 activity, our results revealed that the Samd14-CP interaction is a determinant of erythroid precursor cell levels and function. Samd14-CP promotes SCF/Kit signaling in CD71med spleen erythroid precursors. Given the roles of Kit signaling in hematopoiesis and Samd14 in Kit pathway activation, this mechanism may have pathological implications in acute/chronic anemia.