Pigment cell progenitor heterogeneity and reiteration of developmental signaling underlie melanocyte regeneration in zebrafish

Abstract

Tissue-resident stem and progenitor cells are present in many adult organs, where they are important for organ homeostasis and repair in response to injury. However, the signals that activate these cells and the mechanisms governing how these cells renew or differentiate are highly context-dependent and incompletely understood, particularly in non-hematopoietic tissues. In the skin, melanocyte stem and progenitor cells are responsible for replenishing mature pigmented melanocytes. In mammals, these cells reside in the hair follicle bulge and bulb niches where they are activated during homeostatic hair follicle turnover and following melanocyte destruction, as occurs in vitiligo and other skin hypopigmentation disorders. Recently, we identified melanocyte progenitors in adult zebrafish skin. To elucidate mechanisms governing melanocyte progenitor renewal and differentiation we analyzed individual transcriptomes from thousands of melanocyte lineage cells during the regeneration process. We identified transcriptional signatures for progenitors, deciphered transcriptional changes and intermediate cell states during regeneration, and analyzed cell-cell signaling changes to discover mechanisms governing melanocyte regeneration. We identified KIT signaling via the RAS/MAPK pathway as a regulator of melanocyte progenitor direct differentiation and asymmetric division. Our findings show how activation of different subpopulations of mitfa-positive cells underlies cellular transitions required to properly reconstitute the melanocyte pigmentary system following injury.

Data availability

Sequencing data have been deposited in GEO under accession code: GSE190115.Other Source Data files have been provided for individual figures.

The following data sets were generated

Article and author information

Author details

  1. William Tyler Frantz

    Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1207-9652
  2. Sharanya Iyengar PhD

    Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. James Neiswender PhD

    Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Alyssa Cousineau

    Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. René Maehr

    Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9520-3382
  6. Craig J Ceol

    Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, United States
    For correspondence
    craig.ceol@umassmed.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7188-7580

Funding

National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01 AR081355)

  • William Tyler Frantz
  • Craig J Ceol

National Institute of General Medical Sciences (T32 GM107000)

  • William Tyler Frantz

National Cancer Institute (T32 CA130807)

  • William Tyler Frantz

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

Reviewing Editor

  1. David M Parichy, University of Virginia, United States

Ethics

Animal experimentation: Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. Zebrafish were handled in accordance with protocols approved by the University of Massachusetts Medical School IACUC protocol (A-2171). For procedures, including imaging and genotyping, animals were anesthetized in 0.17% tricaine or euthanized by overdose of tricaine. Every effort was made to minimize suffering.

Version history

  1. Received: March 25, 2022
  2. Preprint posted: April 29, 2022 (view preprint)
  3. Accepted: March 31, 2023
  4. Accepted Manuscript published: April 6, 2023 (version 1)
  5. Version of Record published: April 26, 2023 (version 2)

Copyright

© 2023, Frantz 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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  1. William Tyler Frantz
  2. Sharanya Iyengar PhD
  3. James Neiswender PhD
  4. Alyssa Cousineau
  5. René Maehr
  6. Craig J Ceol
(2023)
Pigment cell progenitor heterogeneity and reiteration of developmental signaling underlie melanocyte regeneration in zebrafish
eLife 12:e78942.
https://doi.org/10.7554/eLife.78942

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https://doi.org/10.7554/eLife.78942

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