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Dissection of melanocyte stem cell transcriptomes during melanocyte regeneration in adult zebrafish

ABSTRACT: To elucidate mechanisms governing McSC self-renewal and differentiation we analyzed individual transcriptomes from thousands of melanocyte lineage cells during the regeneration process. We identified transcriptional signatures for McSCs, deciphered transcriptional changes and intermediate cell states during regeneration, and analyzed cell-cell signaling changes to discover mechanisms governing melanocyte regeneration.

ORGANISM(S): Danio rerio

PROVIDER: GSE190115 | GEO | 2023/04/18

REPOSITORIES: GEO

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Quietly hiding: PD-L1 checkpoint expression in melanocyte stem cell quiescence and aging

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Sexual dimorphism in melanocyte stem cell behavior reveals combinational therapeutic strategies for cutaneous repigmentation [scRNA-seq]

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Sexual dimorphism in melanocyte stem cell behavior reveals combinational therapeutic strategies for cutaneous repigmentation [RNA-Seq]

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Dissection of melanocyte stem cell transcriptomes during melanocyte regeneration in adult zebrafish

Project description:Dissection of melanocyte stem cell transcriptomes during melanocyte regeneration in adult zebrafish

| PRJNA785890 | ENA

BMP signaling: at the gate between activated melanocyte stem cells and differentiation [ATAC-seq]

Project description:Through recurrent bouts synchronous with the hair cycle, quiescent melanocyte stem cells (McSCs) become activated to generate proliferative progeny that differentiate into pigment-producing melanocytes. The signaling factors orchestrating these events remain incompletely understood. Here, we use single cell RNA-sequencing with comparative gene expression analysis to elucidate the transcriptional dynamics of McSCs through quiescence, activation, and melanocyte maturation. Unearthing signs of increased WNT and BMP signaling along this progression, we endeavored to understand how these pathways are integrated during differentiation. Employing conditional lineage-specific genetic ablation studies in mice, we find that loss of BMP signaling in the lineage leads to hair graying due to a block in melanocyte maturation. We show that interestingly, BMP signaling functions downstream of activated McSCs and maintains WNT effector, transcription factor LEF1. Employing pseudotime analysis, genetics, and promoter analyses, and chromatin landscaping, we show that following WNT-mediated activation of McSCs, BMP and WNT pathways collaborate to trigger the commitment of proliferative progeny by fueling LEF1 and MITF-dependent differentiation. Our findings shed light upon the signaling interplay and timing of cues that orchestrate melanocyte lineage progression in the hair follicle and underscore a key role for BMP signaling in driving complete differentiation.

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