Cross-tissue organization of the fibroblast lineage

Matthew B. Buechler, Rachana N. Pradhan, Akshay T. Krishnamurty, Christian Cox, Aslihan Karabacak Calviello, Amber W. Wang, Yeqing Angela Yang, Lucinda Tam, Roger Caothien, Merone Roose-Girma, Zora Modrusan, Joseph R. Arron, Richard Bourgon (), Sören Müller () and Shannon. J. Turley ()
Additional contact information
Matthew B. Buechler: Genentech
Rachana N. Pradhan: Genentech
Akshay T. Krishnamurty: Genentech
Christian Cox: Genentech
Aslihan Karabacak Calviello: Genentech
Amber W. Wang: Genentech
Yeqing Angela Yang: Genentech
Lucinda Tam: Genentech
Roger Caothien: Genentech
Merone Roose-Girma: Genentech
Zora Modrusan: Genentech
Joseph R. Arron: Genentech
Richard Bourgon: Genentech
Sören Müller: Genentech
Shannon. J. Turley: Genentech

Nature, 2021, vol. 593, issue 7860, 575-579

Abstract: Abstract 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 healing1. Recent studies have described fibroblast heterogeneity within individual tissues1. 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 DptIRESCreERT2 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.

Date: 2021
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DOI: 10.1038/s41586-021-03549-5

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