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Single-cell transcriptomic analysis of small and large wounds reveals the distinct spatial organization of regenerative fibroblasts.
Phan, Quan M; Sinha, Sarthak; Biernaskie, Jeff; Driskell, Ryan R.
Afiliación
  • Phan QM; School of Molecular Biosciences, Washington State University, Pullman, WA, USA.
  • Sinha S; Department of Comparative Biology and Experimental Medicine, Faculty of Veterinary Medicine, University of Calgary, Calgary, AB, Canada.
  • Biernaskie J; Department of Surgery, Cumming School of Medicine, Alberta Children's Hospital Research Institute, Hotchkiss Brain Institute University of Calgary, Calgary, AB, Canada.
  • Driskell RR; School of Molecular Biosciences, Washington State University, Pullman, WA, USA.
Exp Dermatol ; 30(1): 92-101, 2021 01.
Article en En | MEDLINE | ID: mdl-33237598
Wound-induced hair follicle neogenesis (WIHN) has been an important model to study hair follicle regeneration during wound repair. However, the cellular and molecular components of the dermis that make large wounds more regenerative are not fully understood. Here, we compare and contrast recently published scRNA-seq data of small scarring wounds to wounds that regenerate in hope to elucidate the role of fibroblasts lineages in WIHN. Our analysis revealed an over-representation of the newly identified upper wound fibroblasts in regenerative wound conditions, which express the retinoic acid binding protein Crabp1. This regenerative cell type shares a similar gene signature to the murine papillary fibroblast lineage, which are necessary to support hair follicle morphogenesis and homeostasis. RNA velocity analysis comparing scarring and regenerating wounds revealed the divergent trajectories towards upper and lower wound fibroblasts and that the upper populations were closely associated with the specialized dermal papilla. We also provide analyses and explanation reconciling the inconsistency between the histological lineage tracing and the scRNA-seq data from recent reports investigating large wounds. Finally, we performed a computational test to map the spatial location of upper wound fibroblasts in large wounds which revealed that upper peripheral fibroblasts might harbour equivalent regenerative competence as those in the centre. Overall, our scRNA-seq reanalysis combining multiple samples suggests that upper wound fibroblasts are required for hair follicle regeneration and that papillary fibroblasts may migrate from the wound periphery to the centre during wound re-epithelialization. Moreover, data from this publication are made available on our searchable web resource: https://skinregeneration.org/.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Cicatrización de Heridas / Heridas y Lesiones / Cicatriz / Transcriptoma / Fibroblastos Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Exp Dermatol Asunto de la revista: DERMATOLOGIA Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Cicatrización de Heridas / Heridas y Lesiones / Cicatriz / Transcriptoma / Fibroblastos Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Exp Dermatol Asunto de la revista: DERMATOLOGIA Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos
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