Pigment cell progenitor heterogeneity and reiteration of developmental signaling underlie melanocyte regeneration in zebrafish
- University of Massachusetts Medical School, United States
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.
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Dissection of melanocyte stem cell transcriptomes during melanocyte regeneration in adult zebrafishNCBI Gene Expression Omnibus, GSE190115.
Article and author information
Author details
William Tyler Frantz
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.
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.
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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Pigment cell progenitor heterogeneity and reiteration of developmental signaling underlie melanocyte regeneration in zebrafish
eLife 12:e78942.
https://doi.org/10.7554/eLife.78942
