Single-cell and spatial multi-omics highlight effects of anti-integrin therapy across cellular compartments in ulcerative colitis

Nat Commun. 2024 Feb 19;15(1):1493. doi: 10.1038/s41467-024-45665-6.

Elvira Mennillo ¹, Yang Joon Kim ², Gyehyun Lee ¹, Iulia Rusu ¹, Ravi K Patel ¹ ³, Leah C Dorman ², Emily Flynn ³, Stephanie Li ¹, Jared L Bain ¹, Christopher Andersen ¹ ³, Arjun Rao ¹ ³, Stanley Tamaki ³, Jessica Tsui ¹ ³ ⁴, Alan Shen ¹ ³ ⁴, Madison L Lotstein ¹ ³, Maha Rahim ⁵, Mohammad Naser ⁶, Faviola Bernard-Vazquez ¹, Walter Eckalbar ³, Soo-Jin Cho ⁴, Kendall Beck ¹, Najwa El-Nachef ¹, Sara Lewin ¹, Daniel R Selvig ¹, Jonathan P Terdiman ¹, Uma Mahadevan ¹, David Y Oh ¹ ⁷, Gabriela K Fragiadakis ¹ ³, Angela Pisco ², Alexis J Combes ¹ ³ ⁴, Michael G Kattah ⁸

Affiliations

1 Department of Medicine, University of California San Francisco, San Francisco, CA, USA.
2 Chan Zuckerberg Biohub, San Francisco, CA, USA.
3 CoLabs, University of California San Francisco, San Francisco, CA, USA.
4 Department of Pathology, University of California San Francisco, San Francisco, CA, 94143, USA.
5 Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, 94143, USA.
6 Biological Imaging Development CoLab, University of California San Francisco, San Francisco, CA, USA.
7 Division of Hematology/Oncology, Department of Medicine, University of California San Francisco, San Francisco, CA, USA.
8 Department of Medicine, University of California San Francisco, San Francisco, CA, USA. michael.kattah@ucsf.edu.

PMID: 38374043 DOI: 10.1038/s41467-024-45665-6

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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Product Name

Description

Target

Research Area
HY-10071

Y-27632

99.91%, Selective ROCK Inhibitor

Organoid; ROCK; Apoptosis

Cancer

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