Charting the cellular biogeography in colitis reveals fibroblast trajectories and coordinated spatial remodeling.

Journal

Cell
ISSN: 1097-4172
Titre abrégé: Cell
Pays: United States
ID NLM: 0413066

Informations de publication

Date de publication:
01 Apr 2024
Historique:
received: 20 04 2023
revised: 20 11 2023
accepted: 07 03 2024
medline: 4 4 2024
pubmed: 4 4 2024
entrez: 3 4 2024
Statut: aheadofprint

Résumé

Gut inflammation involves contributions from immune and non-immune cells, whose interactions are shaped by the spatial organization of the healthy gut and its remodeling during inflammation. The crosstalk between fibroblasts and immune cells is an important axis in this process, but our understanding has been challenged by incomplete cell-type definition and biogeography. To address this challenge, we used multiplexed error-robust fluorescence in situ hybridization (MERFISH) to profile the expression of 940 genes in 1.35 million cells imaged across the onset and recovery from a mouse colitis model. We identified diverse cell populations, charted their spatial organization, and revealed their polarization or recruitment in inflammation. We found a staged progression of inflammation-associated tissue neighborhoods defined, in part, by multiple inflammation-associated fibroblasts, with unique expression profiles, spatial localization, cell-cell interactions, and healthy fibroblast origins. Similar signatures in ulcerative colitis suggest conserved human processes. Broadly, we provide a framework for understanding inflammation-induced remodeling in the gut and other tissues.

Identifiants

DOI: 10.1016/j.cell.2024.03.013 PMID: 38569542
pubmed: 38569542
pii: S0092-8674(24)00254-X
doi: 10.1016/j.cell.2024.03.013
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

Copyright © 2024 Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests J.R.M. is a co-founder of, stakeholder in, and advisor for Vizgen, Inc. J.R.M. is an inventor on patents associated with MERFISH applied for on his behalf by Harvard University and Boston Children’s Hospital. J.R.M.’s interests were reviewed and are managed by Boston Children’s Hospital in accordance with their conflict-of-interest policies. R.N. is a paid consultant for Quris-AI. V.K.K. has an ownership interest in Tizona Therapeutics, Trishula Therapeutics, Celsius Therapeutics, Bicara Therapeutics, Larkspur Therapeutics. V.K.K. has financial interests in Biocon Biologic, Compass, Elpiscience Biopharmaceutical Ltd, Equilium Inc, PerkinElmer, and Syngene Intl. V.K.K. is a member of SABs for Cell Signaling Technology, Elpiscience Biopharmaceutical Ltd, GlaxoSmithKline, Larkspur, Novartis Sabatolimab, Tizona Therapeutics, Tr1X, and Werewolf. A.C.A. is a member of the SAB for Tizona Therapeutics, Trishula Therapeutics, Compass Therapeutics, Zumutor Biologics, ImmuneOncia, and Nekonal Sarl. A.C.A. is also a paid consultant for iTeos Therapeutics, Larkspur Biosciences, and Excepgen. R.N., V.K.K., and A.C.A.’s interests were reviewed and managed by Mass General Brigham in accordance with their conflict-of-interest policies.

Auteurs

Paolo Cadinu (P)

Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA 02115, USA; Department of Microbiology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA.

Kisha N Sivanathan (KN)

Gene Lay Institute of Immunology and Inflammation, Brigham and Women's Hospital, Mass General Hospital, and Harvard Medical School, Boston, MA 02115, USA; Ann Romney Center for Neurologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA 02115, USA; Department of Immunology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA.

Aditya Misra (A)

Gene Lay Institute of Immunology and Inflammation, Brigham and Women's Hospital, Mass General Hospital, and Harvard Medical School, Boston, MA 02115, USA; Ann Romney Center for Neurologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA 02115, USA; Department of Immunology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA.

Rosalind J Xu (RJ)

Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA 02115, USA; Department of Microbiology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA; Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA.

Davide Mangani (D)

Gene Lay Institute of Immunology and Inflammation, Brigham and Women's Hospital, Mass General Hospital, and Harvard Medical School, Boston, MA 02115, USA; Ann Romney Center for Neurologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA 02115, USA.

Evan Yang (E)

Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA 02115, USA; Department of Microbiology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA.

Joseph M Rone (JM)

Gene Lay Institute of Immunology and Inflammation, Brigham and Women's Hospital, Mass General Hospital, and Harvard Medical School, Boston, MA 02115, USA; Ann Romney Center for Neurologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA 02115, USA; Department of Immunology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA.

Katherine Tooley (K)

Gene Lay Institute of Immunology and Inflammation, Brigham and Women's Hospital, Mass General Hospital, and Harvard Medical School, Boston, MA 02115, USA; Ann Romney Center for Neurologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA 02115, USA.

Yoon-Chul Kye (YC)

Gene Lay Institute of Immunology and Inflammation, Brigham and Women's Hospital, Mass General Hospital, and Harvard Medical School, Boston, MA 02115, USA; Ann Romney Center for Neurologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA 02115, USA.

Lloyd Bod (L)

Gene Lay Institute of Immunology and Inflammation, Brigham and Women's Hospital, Mass General Hospital, and Harvard Medical School, Boston, MA 02115, USA; Ann Romney Center for Neurologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA 02115, USA.

Ludwig Geistlinger (L)

Center for Computational Biomedicine, Harvard Medical School, Boston, MA 02115, USA.

Tyrone Lee (T)

Center for Computational Biomedicine, Harvard Medical School, Boston, MA 02115, USA.

Randall T Mertens (RT)

Gene Lay Institute of Immunology and Inflammation, Brigham and Women's Hospital, Mass General Hospital, and Harvard Medical School, Boston, MA 02115, USA; Ann Romney Center for Neurologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA 02115, USA; Department of Immunology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA.

Noriaki Ono (N)

University of Texas Health Science Center at Houston School of Dentistry, Houston, TX 77030, USA.

Gang Wang (G)

Department of Immunology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA.

Liliana Sanmarco (L)

Gene Lay Institute of Immunology and Inflammation, Brigham and Women's Hospital, Mass General Hospital, and Harvard Medical School, Boston, MA 02115, USA; Ann Romney Center for Neurologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA 02115, USA.

Francisco J Quintana (FJ)

Gene Lay Institute of Immunology and Inflammation, Brigham and Women's Hospital, Mass General Hospital, and Harvard Medical School, Boston, MA 02115, USA; Ann Romney Center for Neurologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA 02115, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.

Ana C Anderson (AC)

Gene Lay Institute of Immunology and Inflammation, Brigham and Women's Hospital, Mass General Hospital, and Harvard Medical School, Boston, MA 02115, USA; Ann Romney Center for Neurologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA 02115, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.

Vijay K Kuchroo (VK)

Gene Lay Institute of Immunology and Inflammation, Brigham and Women's Hospital, Mass General Hospital, and Harvard Medical School, Boston, MA 02115, USA; Ann Romney Center for Neurologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA 02115, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.

Jeffrey R Moffitt (JR)

Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA 02115, USA; Department of Microbiology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA. Electronic address: jeffrey.moffitt@childrens.harvard.edu.

Roni Nowarski (R)

Gene Lay Institute of Immunology and Inflammation, Brigham and Women's Hospital, Mass General Hospital, and Harvard Medical School, Boston, MA 02115, USA; Ann Romney Center for Neurologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA 02115, USA; Department of Immunology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA. Electronic address: rnowarski@bwh.harvard.edu.

Classifications MeSH