期刊
NATURE COMMUNICATIONS
卷 10, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/s41467-018-08247-x
关键词
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资金
- Pew Charitable Trust
- NIH [R01-AR067273, R01-AR069653, U01-AR073159, R01-AR055309, R01-AI047833]
- NIH Skin Diseases Research Core grant [P30-AR057217]
- NSF [DMS1562176, DMS1763272]
- Simons Foundation Grant [594598]
- NSF-GRFP [DGE-1321846]
- MBRS-IMSD training grant [GM055246]
- Howard Scheidermann Fellowship Award
- University of California President's Postdoctoral Fellowship Program
- Canadian Institutes of Health Research Postdoctoral Fellowship
- UCI Stem Cell Research Center seed grant
- UCI Skin Center pilot grant
- UCI Center for Complex Biological Systems (CCBS) opportunity award
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.
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