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Cited by 62melanin and skin pigmentationHair Growth and DisordersMelanoma and MAPK Pathways

BMP signaling: at the gate between activated melanocyte stem cells and differentiation

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Infarinato, Nicole R., Stewart, Katherine S., Yang, Yihao, Gomez, Nicholas C., Pasolli, H. Amalia, Hidalgo, Lynette, Polak, Lisa, Carroll, Thomas S. +1 more·2020·Genes & Development
DOI 10.1101/gad.340281.120PMC PMC7706702
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Abstract

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 converging signs of increased WNT and BMP signaling along this progression, we endeavored to understand how these pathways are integrated. Employing conditional lineage-specific genetic ablation studies in mice, we found 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 from activated McSCs and maintains WNT effector, transcription factor LEF1. Employing pseudotime analysis, genetics, 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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  • BMP also promotes postnatal differentiation of WNT-activated hair follicle stem cells as melanocytes, with progenitors accumulating in excess if BMP signaling is blocked.

    “Yet BMP also promotes postnatal differentiation of WNT-activated hair follicle stem cells as melanocytes, with progenitors accumulating in excess if BMP signaling is blocked (37).”

    From Agouti and BMP signaling drive a naturally occurring fate conversion of melanophores to leucophores in zebrafish (2025) · cites this paper as [37]

    The Results report that BMP signaling promotes maturation of melanocyte stem-cell progeny and that blocking it increases the number of less-differentiated cells in mouse hair bulbs. However, the paper distinguishes melanocyte stem cells from epithelial hair follicle stem cells; it does not say that the latter differentiate into melanocytes. Page numbers are unavailable in our copy. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

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Sorted by citations

Authors
Infarinato, N. R., Stewart, K. S., Yang, Y., Gomez, N. C., Pasolli, H. A., Hidalgo, L., Polak, L., Carroll, T. S., & Fuchs, E.
Affiliations
  • Howard Hughes Medical Institute (US)
  • Rockefeller University (US)
ORCID
Venue
Genes & Development
Publisher
Cold Spring Harbor Laboratory
Published
2020-11-12
Volume
34
Issue
23-24
Pages
1713-1734
ISSN
  • 0890-9369 (ISSN-L)
  • 1549-5477
DOI
10.1101/gad.340281.120
PMC
PMC7706702
OpenAlex
W3102072634
Cited by
62
References
6
Citations by year
2026: 8 · 2025: 10 · 2024: 15 · 2023: 20 · 2022: 5 · 2021: 4
Type
posted content
Language
en
Open access
Licence
cc-by-nc
Locations
  • Genes & Development (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • HighWire Press Open Archive (submittedVersion)
Funders
  • National Institute of Arthritis and Musculoskeletal and Skin Diseases (F31AR073110)
  • Canadian Institute of Health Research
  • National Cancer Institute (F32CA221353)
  • Burroughs Wellcome Fund
  • National Institutes of Health (AR050452)
  • Melanoma Research Alliance
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › melanin and skin pigmentation
  • Health Sciences › Medicine › Urology › Hair Growth and Disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Melanoma and MAPK Pathways
Keywords
BMP signaling, melanocyte stem cells, melanocyte differentiation, Wnt signaling, LEF1, MITF, hair follicle, hair graying, melanocyte lineage, transcriptional dynamics, pseudotime, chromatin accessibility
MeSH terms
Animals, Cell Differentiation, Melanocytes, Stem Cells, Signal Transduction, Cell Lineage, Bone Morphogenetic Proteins, Gene Expression Profiling, Mice, Microphthalmia-Associated Transcription Factor, Lymphoid Enhancer-Binding Factor 1, Single-Cell Analysis

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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