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Cross-tissue organization of the fibroblast lineage

Author

Listed:
  • 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)

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.

Suggested Citation

  • 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, 2021. "Cross-tissue organization of the fibroblast lineage," Nature, Nature, vol. 593(7860), pages 575-579, May.
  • Handle: RePEc:nat:nature:v:593:y:2021:i:7860:d:10.1038_s41586-021-03549-5
    DOI: 10.1038/s41586-021-03549-5
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    3. Christopher J. Hanley & Sara Waise & Matthew J. Ellis & Maria A. Lopez & Wai Y. Pun & Julian Taylor & Rachel Parker & Lucy M. Kimbley & Serena J. Chee & Emily C. Shaw & Jonathan West & Aiman Alzetani , 2023. "Single-cell analysis reveals prognostic fibroblast subpopulations linked to molecular and immunological subtypes of lung cancer," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
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    14. Shimrit Mayer & Tomer Milo & Achinoam Isaacson & Coral Halperin & Shoval Miyara & Yaniv Stein & Chen Lior & Meirav Pevsner-Fischer & Eldad Tzahor & Avi Mayo & Uri Alon & Ruth Scherz-Shouval, 2023. "The tumor microenvironment shows a hierarchy of cell-cell interactions dominated by fibroblasts," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
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    17. Seongryong Kim & Ji Hyang Jeon & Myeonghwan Kim & Yeji Lee & Yun-Ho Hwang & Myungsun Park & C. Han Li & Taeyoung Lee & Jung-Ah Lee & You-Me Kim & Dokeun Kim & Hyukjin Lee & You-Jin Kim & V. Narry Kim , 2024. "Innate immune responses against mRNA vaccine promote cellular immunity through IFN-β at the injection site," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
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    19. LiangYu Zhao & Sha Han & HengChuan Su & JianYing Li & ErLei Zhi & Peng Li & ChenCheng Yao & RuHui Tian & HuiXing Chen & HuiRong Chen & JiaQiang Luo & ChenKun Shi & ZhiYong Ji & JianLin Hu & Gang Wu & , 2022. "Single-cell transcriptome atlas of the human corpus cavernosum," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
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    23. Urban Lendahl & Lars Muhl & Christer Betsholtz, 2022. "Identification, discrimination and heterogeneity of fibroblasts," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    24. Lena Cords & Sandra Tietscher & Tobias Anzeneder & Claus Langwieder & Martin Rees & Natalie Souza & Bernd Bodenmiller, 2023. "Cancer-associated fibroblast classification in single-cell and spatial proteomics data," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
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