Distinct melanocyte subpopulations defined by stochastic expression of proliferation or maturation programs enable a rapid and sustainable pigmentation response
| Author(s) | Aggarwal, Ayush | |
| Author(s) | Nasreen, Ayesha | |
| Author(s) | Sharma, Babita | |
| Author(s) | Sahoo, Sarthak | |
| Author(s) | Aswin, Keerthic | |
| Author(s) | Faruq, Mohammed | |
| Author(s) | Pandey, Rajesh | |
| Author(s) | Jolly, Mohit K. | |
| Author(s) | Singh, Abhyudai | |
| Author(s) | Gokhale, Rajesh S. | |
| Author(s) | Natarajan, Vivek T. | |
| Date Accessioned | 2024-09-06T18:11:38Z | |
| Date Available | 2024-09-06T18:11:38Z | |
| Publication Date | 2024-08-20 | |
| Description | This article was originally published in PLoS Biology. The version of record is available at: https://doi.org/10.1371/journal.pbio.3002776 © 2024 Aggarwal et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. | |
| Abstract | The ultraviolet (UV) radiation triggers a pigmentation response in human skin, wherein, melanocytes rapidly activate divergent maturation and proliferation programs. Using single-cell sequencing, we demonstrate that these 2 programs are segregated in distinct subpopulations in melanocytes of human and zebrafish skin. The coexistence of these 2 cell states in cultured melanocytes suggests possible cell autonomy. Luria–Delbrück fluctuation test reveals that the initial establishment of these states is stochastic. Tracking of pigmenting cells ascertains that the stochastically acquired state is faithfully propagated in the progeny. A systemic approach combining single-cell multi-omics (RNA+ATAC) coupled to enhancer mapping with H3K27 acetylation successfully identified state-specific transcriptional networks. This comprehensive analysis led to the construction of a gene regulatory network (GRN) that under the influence of noise, establishes a bistable system of pigmentation and proliferation at the population level. This GRN recapitulates melanocyte behaviour in response to external cues that reinforce either of the states. Our work highlights that inherent stochasticity within melanocytes establishes dedicated states, and the mature state is sustained by selective enhancers mark through histone acetylation. While the initial cue triggers a proliferation response, the continued signal activates and maintains the pigmenting subpopulation via epigenetic imprinting. Thereby our study provides the basis of coexistence of distinct populations which ensures effective pigmentation response while preserving the self-renewal capacity. | |
| Sponsor | Funding: VTN secured funding for this project. The Grant number is MLP2008 (project Regen-X). Funder - Council of Scientific and Industrial Research (CSIR) URL of the Funder - https://www.csir.res.in/ The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing interests: RSG is the co-founder of Vyome Biosciences Pvt Ltd., a biopharmaceutical company working in the area of dermatology. Other authors declare no competing interest. | |
| Citation | Aggarwal A, Nasreen A, Sharma B, Sahoo S, Aswin K, Faruq M, et al. (2024) Distinct melanocyte subpopulations defined by stochastic expression of proliferation or maturation programs enable a rapid and sustainable pigmentation response. PLoS Biol 22(8): e3002776. https://doi.org/10.1371/journal.pbio.3002776 | |
| ISSN | 1545-7885 | |
| URL | https://udspace.udel.edu/handle/19716/34925 | |
| Language | en_US | |
| Publisher | PLoS Biology | |
| dc.rights | Attribution 4.0 International | en |
| dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | |
| Title | Distinct melanocyte subpopulations defined by stochastic expression of proliferation or maturation programs enable a rapid and sustainable pigmentation response | |
| Type | Article |
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