Skin vasculature and hair follicle cross-talking associated with stem cell activation and tissue homeostasis

  1. Kefei Nina Li
  2. Prachi Jain
  3. Catherine Hua He
  4. Flora Chae Eun
  5. Sangjo Kang
  6. Tudorita Tumbar  Is a corresponding author
  1. Cornell University, Ithaca, United States

Abstract

Skin vasculature cross-talking with hair follicle stem cells (HFSCs) is poorly understood. Skin vasculature undergoes dramatic remodeling during adult mouse hair cycle. Specifically, a horizontal plexus under the secondary hair germ (HPuHG) transiently neighbors the HFSC activation zone during the quiescence phase (telogen). Increased density of HPuHG can be induced by reciprocal mutations in the epithelium (Runx1) and endothelium (Alk1) in adult mice, and is accompanied by prolonged HFSC quiescence and by delayed entry and progression into the hair growth phase (anagen). Suggestively, skin vasculature produces BMP4, a well-established HFSC quiescence-inducing factor, thus contributing to a proliferation-inhibitory environment near the HFSC. Conversely, the HFSC activator Runx1 regulates secreted proteins with previously demonstrated roles in vasculature remodeling. We suggest a working model in which coordinated remodeling and molecular cross-talking of the adult epithelial and endothelial skin compartments modulate timing of HFSC activation from quiescence for proper tissue homeostasis of adult skin.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files

Article and author information

Author details

  1. Kefei Nina Li

    Molecular Biology and Genetics, Cornell University, Ithaca, Ithaca, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Prachi Jain

    Molecular Biology and Genetics, Cornell University, Ithaca, Ithaca, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Catherine Hua He

    Molecular Biology and Genetics, Cornell University, Ithaca, Ithaca, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Flora Chae Eun

    Molecular Biology and Genetics, Cornell University, Ithaca, Ithaca, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Sangjo Kang

    Molecular Biology and Genetics, Cornell University, Ithaca, Ithaca, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Tudorita Tumbar

    Molecular Biology and Genetics, Cornell University, Ithaca, Ithaca, United States
    For correspondence
    tt252@cornell.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2273-1889

Funding

National Institute of Arthritis and Musculoskeletal and Skin Diseases (RO1 AR070157)

  • Tudorita Tumbar

NYSTEM (DOH01-C30293GG-3450000)

  • Prachi Jain

National Institute of Arthritis and Musculoskeletal and Skin Diseases (AR073806)

  • Tudorita Tumbar

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: Mouse work followed the Cornell University Institutional Animal Care and Use Committee guidelines. IACUC protocol # 2007-0125.

Reviewing Editor

  1. Valerie Horsley, Yale University, United States

Publication history

  1. Received: February 10, 2019
  2. Accepted: July 25, 2019
  3. Accepted Manuscript published: July 25, 2019 (version 1)
  4. Version of Record published: August 6, 2019 (version 2)

Copyright

© 2019, Li 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

  • 3,378
    Page views
  • 534
    Downloads
  • 37
    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. Kefei Nina Li
  2. Prachi Jain
  3. Catherine Hua He
  4. Flora Chae Eun
  5. Sangjo Kang
  6. Tudorita Tumbar
(2019)
Skin vasculature and hair follicle cross-talking associated with stem cell activation and tissue homeostasis
eLife 8:e45977.
https://doi.org/10.7554/eLife.45977

Further reading

    1. Stem Cells and Regenerative Medicine
    Ece Yildiz, Gaby El Alam ... Kristina Schoonjans
    Research Article Updated

    During severe or chronic hepatic injury, biliary epithelial cells (BECs) undergo rapid activation into proliferating progenitors, a crucial step required to establish a regenerative process known as ductular reaction (DR). While DR is a hallmark of chronic liver diseases, including advanced stages of non-alcoholic fatty liver disease (NAFLD), the early events underlying BEC activation are largely unknown. Here, we demonstrate that BECs readily accumulate lipids during high-fat diet feeding in mice and upon fatty acid treatment in BEC-derived organoids. Lipid overload induces metabolic rewiring to support the conversion of adult cholangiocytes into reactive BECs. Mechanistically, we found that lipid overload activates the E2F transcription factors in BECs, which drive cell cycle progression while promoting glycolytic metabolism. These findings demonstrate that fat overload is sufficient to reprogram BECs into progenitor cells in the early stages of NAFLD and provide new insights into the mechanistic basis of this process, revealing unexpected connections between lipid metabolism, stemness, and regeneration.

    1. Stem Cells and Regenerative Medicine
    Dennis May, Sangwon Yun ... Valentina Greco
    Research Article Updated

    Stem cell differentiation requires dramatic changes in gene expression and global remodeling of chromatin architecture. How and when chromatin remodels relative to the transcriptional, behavioral, and morphological changes during differentiation remain unclear, particularly in an intact tissue context. Here, we develop a quantitative pipeline which leverages fluorescently-tagged histones and longitudinal imaging to track large-scale chromatin compaction changes within individual cells in a live mouse. Applying this pipeline to epidermal stem cells, we reveal that cell-to-cell chromatin compaction heterogeneity within the stem cell compartment emerges independent of cell cycle status, and instead is reflective of differentiation status. Chromatin compaction state gradually transitions over days as differentiating cells exit the stem cell compartment. Moreover, establishing live imaging of Keratin-10 (K10) nascent RNA, which marks the onset of stem cell differentiation, we find that Keratin-10 transcription is highly dynamic and largely precedes the global chromatin compaction changes associated with differentiation. Together, these analyses reveal that stem cell differentiation involves dynamic transcriptional states and gradual chromatin rearrangement.