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Single-cell analysis reveals fibroblast heterogeneity and myeloid-derived adipocyte progenitors in murine skin wounds.

Christian F Guerrero-Juarez | Priya H Dedhia | Suoqin Jin | Rolando Ruiz-Vega | Dennis Ma | Yuchen Liu | Kosuke Yamaga | Olga Shestova | Denise L Gay | Zaixin Yang | Kai Kessenbrock | Qing Nie | Warren S Pear | George Cotsarelis | Maksim V Plikus
Nature communications | 2019

During wound healing in adult mouse skin, hair follicles and then adipocytes regenerate. Adipocytes regenerate from myofibroblasts, a specialized contractile wound fibroblast. Here we study wound fibroblast diversity using single-cell RNA-sequencing. On analysis, wound fibroblasts group into twelve clusters. Pseudotime and RNA velocity analyses reveal that some clusters likely represent consecutive differentiation states toward a contractile phenotype, while others appear to represent distinct fibroblast lineages. One subset of fibroblasts expresses hematopoietic markers, suggesting their myeloid origin. We validate this finding using single-cell western blot and single-cell RNA-sequencing on genetically labeled myofibroblasts. Using bone marrow transplantation and Cre recombinase-based lineage tracing experiments, we rule out cell fusion events and confirm that hematopoietic lineage cells give rise to a subset of myofibroblasts and rare regenerated adipocytes. In conclusion, our study reveals that wounding induces a high degree of heterogeneity among fibroblasts and recruits highly plastic myeloid cells that contribute to adipocyte regeneration.

Pubmed ID: 30737373

Research resources used in this publication

None found

Antibodies used in this publication

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Associated grants

  • Agency: NIAID NIH HHS, United States
    Id: R01 AI047833
  • Agency: NIAMS NIH HHS, United States
    Id: R01 AR067273
  • Agency: NIAMS NIH HHS, United States
    Id: U01 AR073159
  • Agency: NIAMS NIH HHS, United States
    Id: R01 AR055309
  • Agency: NIAMS NIH HHS, United States
    Id: R01 AR069653
  • Agency: NIAMS NIH HHS, United States
    Id: P30 AR057217
  • Agency: NIGMS NIH HHS, United States
    Id: R25 GM055246

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AnimalTFDB (tool)

RRID:SCR_001624

A comprehensive transcription factor (TF) database in which they identified and classified all the genome-wide TFs in 50 sequenced animal genomes (Ensembl release version 60). In addition to TFs, it also collects transcription co-factors and chromatin remodeling factors of those genomes, which play regulatory roles in transcription. Here they defined the TFs as proteins containing a sequence-specific DNA-binding domain (DBD) and regulating target gene expression. Currently, the AnimalTFDB classifies all the animal TFs into 72 families according to their conserved DBDs. Gene lists of transcription factors, transcription co-factors and chromatin remodeling factors of each species are available for downloading.

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RRID:SCR_012931

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