LB1013 Nuclear transcriptomics reveals the determinants of eccrine sweat gland fate and differentiation

نویسندگان

چکیده

Eccrine sweat glands are the predominant ectodermal appendage of human skin and essential in thermoregulation. Despite their importance, developmental program cellular interactions that drive eccrine gland formation poorly understood. In mouse volar skin, to which restricted this species, expression transcription factor Engrailed-1 (En1) basal ectoderm is required for specification placodes, while humans, upregulation EN1 a hallmark eccrine-forming skin. Accordingly, we used En1 as molecular node interrogate program. To end, adapted single-nucleus RNA sequencing technology profile transcriptomes developing wildtype inducible, ectoderm-specific, knock-out mice (cEn1KO). We found cEn1KO characterized by loss subsets keratinocyte dermal nuclei. Computational analyses vivo validation top markers cEn1KO-depleted nuclei revealed signatures progression from placode through nascent differentiation. Moreover, differentially-expressed population, identified, first time, population mesenchymal cells specifically associated with anlage. Targeted ablation using inducible cell type-specific Diphtheria toxin led depletion placodes Our findings reveal novel paradigms driving development, highlight potential nuclear transcriptomics interrogating functional heterogeneity

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ژورنال

عنوان ژورنال: Journal of Investigative Dermatology

سال: 2022

ISSN: ['1523-1747', '0022-202X']

DOI: https://doi.org/10.1016/j.jid.2022.05.1041