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

被引：20

作者：

Mennillo, Elvira ^{[1
]}

Kim, Yang Joon ^{[2
]}

Lee, Gyehyun ^{[1
]}

Rusu, Iulia ^{[1
]}

Patel, Ravi K. ^{[1
,3
]}

Dorman, Leah C. ^{[2
]}

Flynn, Emily ^{[3
]}

Li, Stephanie ^{[1
]}

Bain, Jared L. ^{[1
]}

Andersen, Christopher ^{[1
,3
]}

Rao, Arjun ^{[1
,3
]}

Tamaki, Stanley ^{[3
]}

Tsui, Jessica ^{[1
,3
,4
]}

Shen, Alan ^{[1
,3
,4
]}

Lotstein, Madison L. ^{[1
,3
]}

Rahim, Maha ^{[5
]}

Naser, Mohammad ^{[6
]}

Bernard-Vazquez, Faviola ^{[1
]}

Eckalbar, Walter ^{[3
]}

Cho, Soo-jin ^{[4
]}

Beck, Kendall ^{[1
]}

El-Nachef, Najwa ^{[1
]}

Lewin, Sara ^{[1
]}

Selvig, Daniel R. ^{[1
]}

Terdiman, Jonathan P. ^{[1
]}

Mahadevan, Uma ^{[1
]}

Oh, David Y. ^{[1
,7
]}

Fragiadakis, Gabriela K. ^{[1
,3
]}

Pisco, Angela ^{[2
]}

Combes, Alexis J. ^{[1
,3
,4
]}

Kattah, Michael G. ^{[1
]}

机构：

[1] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA

[2] Chan Zuckerberg Biohub, San Francisco, CA USA

[3] Univ Calif San Francisco, CoLabs, San Francisco, CA 94143 USA

[4] Univ Calif San Francisco, Dept Pathol, San Francisco, CA 94143 USA

[5] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA

[6] Univ Calif San Francisco, Biol Imaging Dev CoLab, San Francisco, CA 94143 USA

[7] Univ Calif San Francisco, Div Hematol Oncol, Dept Med, San Francisco, CA 94143 USA

来源：

NATURE COMMUNICATIONS | 2024年 / 15卷 / 01期

关键词：

REGULATORY T-CELLS; VEDOLIZUMAB; EXPRESSION; RESOLUTION; REVEALS; GENES;

D O I：

10.1038/s41467-024-45665-6

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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 withmodest shifts in lymphocytes. Spatial multi-omics of formalin-fixed biopsies demonstrates trends towards increased abundance and proximity of MNPand 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.

引用

页数：19

共 76 条

[61] Microbial signals, MyD88, and lymphotoxin drive TNF-independent intestinal epithelial tissue damage [J].

Rusu, Iulia ;

Mennillo, Elvira ;

Bain, Jared L. ;

Li, Zhongmei ;

Sun, Xiaofei ;

Ly, Kimberly M. ;

Rosli, Yenny Y. ;

Naser, Mohammad ;

Wang, Zunqiu ;

Advincula, Rommel ;

Achacoso, Philip ;

Shao, Ling ;

Razani, Bahram ;

Klein, Ophir D. ;

Marson, Alexander ;

Turnbaugh, Jessie A. ;

Turnbaugh, Peter J. ;

Malynn, Barbara A. ;

Ma, Averil ;

Kattah, Michael G. .

JOURNAL OF CLINICAL INVESTIGATION, 2022, 132 (05)

[62] Intestinal T Cell Profiling in Inflammatory Bowel Disease: Linking T Cell Subsets to Disease Activity and Disease Course [J].

Smids, Carolijn ;

Horje, Carmen S. Horjus Talabur ;

Drylewicz, Julia ;

Roosenboom, Britt ;

Groenen, Marcel J. M. ;

van Koolwijk, Elly ;

van Lochem, Ellen G. ;

Wahab, Peter J. .

JOURNAL OF CROHNS & COLITIS, 2018, 12 (04) :465-475

[63] Intra- and Inter-cellular Rewiring of the Human Colon during Ulcerative Colitis [J].

Smillie, Christopher S. ;

Biton, Moshe ;

Ordovas-Montanes, Jose ;

Sullivan, Ken M. ;

Burgin, Grace ;

Graham, Daniel B. ;

Herbst, Rebecca H. ;

Rogel, Noga ;

Slyper, Michel ;

Waldman, Julia ;

Sud, Malika ;

Andrews, Elizabeth ;

Velonias, Gabriella ;

Haber, Adam L. ;

Jagadeesh, Karthik ;

Vickovic, Sanja ;

Yao, Junmei ;

Stevens, Christine ;

Dionne, Danielle ;

Nguyen, Lan T. ;

Villani, Alexandra-Chloe ;

Hofree, Matan ;

Creasey, Elizabeth A. ;

Huang, Hailiang ;

Rozenblatt-Rosen, Orit ;

Garber, John J. ;

Khalili, Hamed ;

Desch, A. Nicole ;

Daly, Mark J. ;

Ananthakrishnan, Ashwin N. ;

Shalek, Alex K. ;

Xavier, Ramnik J. ;

Regev, Aviv .

CELL, 2019, 178 (03) :714-+

[64] The Binding Specificity and Selective Antagonism of Vedolizumab, an Anti-α4β7 Integrin Therapeutic Antibody in Development for Inflammatory Bowel Diseases [J].

Soler, Dulce ;

Chapman, Tobias ;

Yang, Li-Li ;

Wyant, Tim ;

Egan, Robert ;

Fedyk, Eric R. .

JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, 2009, 330 (03) :864-875

[65]

Stoeckius M, 2017, NAT METHODS, V14, P865, DOI [10.1038/NMETH.4380, 10.1038/nmeth.4380]

[66]

Van der Auwera Geraldine A, 2013, Curr Protoc Bioinformatics, V43, DOI [10.1002/0471250953.bi1201s43, 10.1002/0471250953.bi1110s43]

[67] Comprehensive Integration of Single-Cell Data [J].

Stuart, Tim ;

Butler, Andrew ;

Hoffman, Paul ;

Hafemeister, Christoph ;

Papalexi, Efthymia ;

Mauck, William M., III ;

Hao, Yuhan ;

Stoeckius, Marlon ;

Smibert, Peter ;

Satija, Rahul .

CELL, 2019, 177 (07) :1888-+

[68] Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles [J].

Subramanian, A ;

Tamayo, P ;

Mootha, VK ;

Mukherjee, S ;

Ebert, BL ;

Gillette, MA ;

Paulovich, A ;

Pomeroy, SL ;

Golub, TR ;

Lander, ES ;

Mesirov, JP .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2005, 102 (43) :15545-15550

[69] FlowSOM: Using self-organizing maps for visualization and interpretation of cytometry data [J].

Van Gassen, Sofie ;

Callebaut, Britt ;

Van Helden, Mary J. ;

Lambrecht, Bart N. ;

Demeester, Piet ;

Dhaene, Tom ;

Saeys, Yvan .

CYTOMETRY PART A, 2015, 87A (07) :636-645

[70] PD-1/PD-L1 blockade abrogates a dysfunctional innate-adaptive immune axis in critical β-coronavirus disease [J].

Vega, Maite Duhalde ;

Olivera, Daniela ;

Davanzo, Gustavo Gastao ;

Bertullo, Mauricio ;

Noya, Veronica ;

de Souza, Gabriela Fabiano ;

Muraro, Stefanie Primon ;

Castro, Icaro ;

Arevalo, Ana Paula ;

Crispo, Martina ;

Galliussi, German ;

Russo, Sofia ;

Charbonnier, David ;

Rammauro, Florencia ;

Jeldres, Mathias ;

Alamon, Catalina ;

Varela, Valentina ;

Batthyany, Carlos ;

Bollati-Fogolin, Mariela ;

Oppezzo, Pablo ;

Pritsch, Otto ;

Proenca-Modena, Jose Luiz ;

Nakaya, Helder I. ;

Trias, Emiliano ;

Barbeito, Luis ;

Anegon, Ignacio ;

Cuturi, Maria Cristina ;

Moraes-Vieira, Pedro ;

Segovia, Mercedes ;

Hill, Marcelo .

SCIENCE ADVANCES, 2022, 8 (38)

← 1 2 3 4 5 6 7 8 →