Rxivist logo

Rxivist combines preprints from bioRxiv with data from Twitter to help you find the papers being discussed in your field. Currently indexing 57,793 bioRxiv papers from 266,023 authors.

Single-cell RNA-seq reveals spatially restricted multicellular fibrotic niches during lung fibrosis

By Nikita Joshi, Satoshi Watanabe, Rohan Verma, Renea P Jablonski, Ching-I Chen, Paul Cheresh, Paul A. Reyfman, Alexandra C. McQuattie-Pimentel, Lango Sichizya, Annette S. Flozak, Cara Gottardi, Carla M Cuda, Harris Perlman, Manu Jain, David W Kamp, GR Scott Budinger, Alexander Misharin

Posted 06 Mar 2019
bioRxiv DOI: 10.1101/569855

Ontologically distinct populations of macrophages differentially contribute to organ fibrosis through unknown mechanisms. We applied lineage tracing, spatial methods and single-cell RNA-seq to a spatially-restricted model of asbestos-induced pulmonary fibrosis. We demonstrate that while tissue-resident interstitial macrophages, tissue-resident alveolar macrophages, and monocyte-derived alveolar macrophages are present in the fibrotic niche, only monocyte-derived alveolar macrophages are causally related to fibrosis. Monocyte-derived alveolar macrophages were specifically localized to fibrotic regions in the proximity of fibroblasts where they expressed molecules known to drive fibroblast proliferation, including PDGFA. Moreover, we identified autocrine M-CSF/M-CSFR signaling in monocyte-derived alveolar macrophages as a novel mechanism promoting their self-maintenance and persistence in the fibrotic niche. Pharmacological blockade of M-CSF signaling led to disappearance of the established population of monocyte-derived alveolar macrophages. Thus, our data indicate that monocyte-derived alveolar macrophages are specifically recruited to the fibrotic niche where they are maintained by autocrine signaling and drive fibrosis by stimulating fibroblast proliferation.

Download data

  • Downloaded 1,053 times
  • Download rankings, all-time:
    • Site-wide: 6,010 out of 57,793
    • In immunology: 71 out of 1,387
  • Year to date:
    • Site-wide: 995 out of 57,793
  • Since beginning of last month:
    • Site-wide: 2,073 out of 57,793

Altmetric data


Downloads over time

Distribution of downloads per paper, site-wide


Sign up for the Rxivist weekly newsletter! (Click here for more details.)


News