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Single-cell and spatial multi-omics highlight effects of anti-integrin therapy across cellular compartments in ulcerative colitis.
Mennillo, Elvira; Kim, Yang Joon; Lee, Gyehyun; Rusu, Iulia; Patel, Ravi K; Dorman, Leah C; Flynn, Emily; Li, Stephanie; Bain, Jared L; Andersen, Christopher; Rao, Arjun; Tamaki, Stanley; Tsui, Jessica; Shen, Alan; Lotstein, Madison L; Rahim, Maha; Naser, Mohammad; Bernard-Vazquez, Faviola; Eckalbar, Walter; Cho, Soo-Jin; Beck, Kendall; El-Nachef, Najwa; Lewin, Sara; Selvig, Daniel R; Terdiman, Jonathan P; Mahadevan, Uma; Oh, David Y; Fragiadakis, Gabriela K; Pisco, Angela; Combes, Alexis J; Kattah, Michael G.
Afiliação
  • Mennillo E; Department of Medicine, University of California San Francisco, San Francisco, CA, USA.
  • Kim YJ; Chan Zuckerberg Biohub, San Francisco, CA, USA.
  • Lee G; Department of Medicine, University of California San Francisco, San Francisco, CA, USA.
  • Rusu I; Department of Medicine, University of California San Francisco, San Francisco, CA, USA.
  • Patel RK; Department of Medicine, University of California San Francisco, San Francisco, CA, USA.
  • Dorman LC; CoLabs, University of California San Francisco, San Francisco, CA, USA.
  • Flynn E; Chan Zuckerberg Biohub, San Francisco, CA, USA.
  • Li S; CoLabs, University of California San Francisco, San Francisco, CA, USA.
  • Bain JL; Department of Medicine, University of California San Francisco, San Francisco, CA, USA.
  • Andersen C; Department of Medicine, University of California San Francisco, San Francisco, CA, USA.
  • Rao A; Department of Medicine, University of California San Francisco, San Francisco, CA, USA.
  • Tamaki S; CoLabs, University of California San Francisco, San Francisco, CA, USA.
  • Tsui J; Department of Medicine, University of California San Francisco, San Francisco, CA, USA.
  • Shen A; CoLabs, University of California San Francisco, San Francisco, CA, USA.
  • Lotstein ML; CoLabs, University of California San Francisco, San Francisco, CA, USA.
  • Rahim M; Department of Medicine, University of California San Francisco, San Francisco, CA, USA.
  • Naser M; CoLabs, University of California San Francisco, San Francisco, CA, USA.
  • Bernard-Vazquez F; Department of Pathology, University of California San Francisco, San Francisco, CA, 94143, USA.
  • Eckalbar W; Department of Medicine, University of California San Francisco, San Francisco, CA, USA.
  • Cho SJ; CoLabs, University of California San Francisco, San Francisco, CA, USA.
  • Beck K; Department of Pathology, University of California San Francisco, San Francisco, CA, 94143, USA.
  • El-Nachef N; Department of Medicine, University of California San Francisco, San Francisco, CA, USA.
  • Lewin S; CoLabs, University of California San Francisco, San Francisco, CA, USA.
  • Selvig DR; Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, 94143, USA.
  • Terdiman JP; Biological Imaging Development CoLab, University of California San Francisco, San Francisco, CA, USA.
  • Mahadevan U; Department of Medicine, University of California San Francisco, San Francisco, CA, USA.
  • Oh DY; CoLabs, University of California San Francisco, San Francisco, CA, USA.
  • Fragiadakis GK; Department of Pathology, University of California San Francisco, San Francisco, CA, 94143, USA.
  • Pisco A; Department of Medicine, University of California San Francisco, San Francisco, CA, USA.
  • Combes AJ; Department of Medicine, University of California San Francisco, San Francisco, CA, USA.
  • Kattah MG; Department of Medicine, University of California San Francisco, San Francisco, CA, USA.
Nat Commun ; 15(1): 1493, 2024 Feb 19.
Article em En | MEDLINE | ID: mdl-38374043
ABSTRACT
Ulcerative colitis (UC) is driven by immune and stromal subsets, culminating in epithelial injury. Vedolizumab (VDZ) is an anti-integrin antibody that is effective for treating UC. VDZ is known to inhibit lymphocyte trafficking to the intestine, but its broader effects on other cell subsets are less defined. To identify the inflammatory cells that contribute to colitis and are affected by VDZ, we perform single-cell transcriptomic and proteomic analyses of peripheral blood and colonic biopsies in healthy controls and patients with UC on VDZ or other therapies. Here we show that VDZ treatment is associated with alterations in circulating and tissue mononuclear phagocyte (MNP) subsets, along with modest shifts in lymphocytes. Spatial multi-omics of formalin-fixed biopsies demonstrates trends towards increased abundance and proximity of MNP and fibroblast subsets in active colitis. Spatial transcriptomics of archived specimens pre-treatment identifies epithelial-, MNP-, and fibroblast-enriched genes related to VDZ responsiveness, highlighting important roles for these subsets in UC.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Colite Ulcerativa Limite: Humans Idioma: En Revista: Nat Commun Assunto da revista: BIOLOGIA / CIENCIA Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Estados Unidos
Texto completo
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Colite Ulcerativa Limite: Humans Idioma: En Revista: Nat Commun Assunto da revista: BIOLOGIA / CIENCIA Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Estados Unidos