Journal
NATURE
Volume 593, Issue 7860, Pages 575-+Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41586-021-03549-5
Keywords
-
Categories
Funding
- Genentech
Ask authors/readers for more resources
Recent studies have identified fibroblast heterogeneity in different tissues, and constructed fibroblast atlases based on single-cell transcriptomic data to reveal universal and activated transcriptional subtypes in healthy and diseased states.
Fibroblasts are non-haematopoietic structural cells that define the architecture of organs, support the homeostasis of tissue-resident cells and have key roles in fibrosis, cancer, autoimmunity and wound healing(1). Recent studies have described fibroblast heterogeneity within individual tissues(1). However, the field lacks a characterization of fibroblasts at single-cell resolution across tissues in healthy and diseased organs. Here we constructed fibroblast atlases by integrating single-cell transcriptomic data from about 230,000 fibroblasts across 17 tissues, 50 datasets, 11 disease states and 2 species. Mouse fibroblast atlases and a Dpt(IRESCreERT2) knock-in mouse identified two universal fibroblast transcriptional subtypes across tissues. Our analysis suggests that these cells can serve as a reservoir that can yield specialized fibroblasts across a broad range of steady-state tissues and activated fibroblasts in disease. Comparison to an atlas of human fibroblasts from perturbed states showed that fibroblast transcriptional states are conserved between mice and humans, including universal fibroblasts and activated phenotypes associated with pathogenicity in human cancer, fibrosis, arthritis and inflammation. In summary, a cross-species and pan-tissue approach to transcriptomics at single-cell resolution has identified key organizing principles of the fibroblast lineage in health and disease.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available