Pigment cell progenitor heterogeneity and reiteration of developmental signaling underlie melanocyte regeneration in zebrafish
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...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2023-04-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/78942 |
| _version_ | 1797838437986861056 |
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| author | William Tyler Frantz Sharanya Iyengar James Neiswender Alyssa Cousineau René Maehr Craig J Ceol |
| author_facet | William Tyler Frantz Sharanya Iyengar James Neiswender Alyssa Cousineau René Maehr Craig J Ceol |
| author_sort | William Tyler Frantz |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-09T15:41:56Z |
| format | Article |
| id | doaj.art-609c615bf2e64daebd889405e7b64582 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-09T15:41:56Z |
| publishDate | 2023-04-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-609c615bf2e64daebd889405e7b645822023-04-27T08:47:53ZengeLife Sciences Publications LtdeLife2050-084X2023-04-011210.7554/eLife.78942Pigment cell progenitor heterogeneity and reiteration of developmental signaling underlie melanocyte regeneration in zebrafishWilliam Tyler Frantz0https://orcid.org/0000-0003-1207-9652Sharanya Iyengar1James Neiswender2Alyssa Cousineau3René Maehr4https://orcid.org/0000-0002-9520-3382Craig J Ceol5https://orcid.org/0000-0002-7188-7580Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, United States; Department of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, United StatesProgram in Molecular Medicine, University of Massachusetts Medical School, Worcester, United States; Department of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, United StatesProgram in Molecular Medicine, University of Massachusetts Medical School, Worcester, United States; Department of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, United StatesProgram in Molecular Medicine, University of Massachusetts Medical School, Worcester, United StatesProgram in Molecular Medicine, University of Massachusetts Medical School, Worcester, United StatesProgram in Molecular Medicine, University of Massachusetts Medical School, Worcester, United States; Department of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, United StatesTissue-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.https://elifesciences.org/articles/78942melanocytesregenerationmelanocyte stem cellsDanio reriostem cell biologyzebrafish |
| spellingShingle | William Tyler Frantz Sharanya Iyengar James Neiswender Alyssa Cousineau René Maehr Craig J Ceol Pigment cell progenitor heterogeneity and reiteration of developmental signaling underlie melanocyte regeneration in zebrafish eLife melanocytes regeneration melanocyte stem cells Danio rerio stem cell biology zebrafish |
| title | Pigment cell progenitor heterogeneity and reiteration of developmental signaling underlie melanocyte regeneration in zebrafish |
| title_full | Pigment cell progenitor heterogeneity and reiteration of developmental signaling underlie melanocyte regeneration in zebrafish |
| title_fullStr | Pigment cell progenitor heterogeneity and reiteration of developmental signaling underlie melanocyte regeneration in zebrafish |
| title_full_unstemmed | Pigment cell progenitor heterogeneity and reiteration of developmental signaling underlie melanocyte regeneration in zebrafish |
| title_short | Pigment cell progenitor heterogeneity and reiteration of developmental signaling underlie melanocyte regeneration in zebrafish |
| title_sort | pigment cell progenitor heterogeneity and reiteration of developmental signaling underlie melanocyte regeneration in zebrafish |
| topic | melanocytes regeneration melanocyte stem cells Danio rerio stem cell biology zebrafish |
| url | https://elifesciences.org/articles/78942 |
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