1. Stem Cells and Regenerative Medicine

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
https://doi.org/10.7554/eLife.45977
Share this article
Cite this article
  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
  2. Download BibTeX
  3. Download .RIS

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

  • 3,067
    Page views
  • 476
    Downloads
  • 29
    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

Categories and tags

Research organism

Further reading

    1. Neuroscience
    2. Stem Cells and Regenerative Medicine

    Generation of vascularized brain organoids to study neurovascular interactions

    Xin-Yao Sun et al.
    Research Article Updated

    Brain organoids have been used to recapitulate the processes of brain development and related diseases. However, the lack of vasculatures, which regulate neurogenesis and brain disorders, limits the utility of brain organoids. In this study, we induced vessel and brain organoids, respectively, and then fused two types of organoids together to obtain vascularized brain organoids. The fused brain organoids were engrafted with robust vascular network-like structures and exhibited increased number of neural progenitors, in line with the possibility that vessels regulate neural development. Fusion organoids also contained functional blood–brain barrier-like structures, as well as microglial cells, a specific population of immune cells in the brain. The incorporated microglia responded actively to immune stimuli to the fused brain organoids and showed ability of engulfing synapses. Thus, the fusion organoids established in this study allow modeling interactions between the neuronal and non-neuronal components in vitro, particularly the vasculature and microglia niche.

    1. Neuroscience
    2. Stem Cells and Regenerative Medicine

    Brain Organoids: Getting the right cells

    Bilal Cakir, In-Hyun Park
    Insight

    Fusing brain organoids with blood vessel organoids leads to the incorporation of non-neural endothelial cells and microglia into the brain organoids.

    1. Computational and Systems Biology
    2. Stem Cells and Regenerative Medicine

    Robotic search for optimal cell culture in regenerative medicine

    Genki N Kanda et al.
    Research Article

    Induced differentiation is one of the most experience- and skill-dependent experimental processes in regenerative medicine, and establishing optimal conditions often takes years. We developed a robotic AI system with a batch Bayesian optimization algorithm that autonomously induces the differentiation of induced pluripotent stem cell-derived retinal pigment epithelial (iPSC-RPE) cells. From 200 million possible parameter combinations, the system performed cell culture in 143 different conditions in 111 days, resulting in 88% better iPSC-RPE production than that obtained by the pre-optimized culture in terms of the pigmentation scores. Our work demonstrates that the use of autonomous robotic AI systems drastically accelerates systematic and unbiased exploration of experimental search space, suggesting immense use in medicine and research.