Intra- and Inter-cellular Rewiring of the Human Colon during Ulcerative Colitis

Christopher S. Smillie; Moshe Biton; Jose Ordovas-Montanes; Keri M. Sullivan; Grace Burgin; Daniel B. Graham; Rebecca H. Herbst; Noga Rogel; Michal Slyper; Julia Waldman; Malika Sud; Elizabeth Andrews; Gabriella Velonias; Adam L. Haber; Karthik Jagadeesh; Sanja Vickovic; Junmei Yao; Christine Stevens; Danielle Dionne; Lan T. Nguyen; Alexandra Chloé Villani; Matan Hofree; Elizabeth A. Creasey; Hailiang Huang; Orit Rozenblatt-Rosen; John J. Garber; Hamed Khalili; A. Nicole Desch; Mark J. Daly; Ashwin N. Ananthakrishnan; Alex K. Shalek; Ramnik J. Xavier; Aviv Regev

doi:10.1016/j.cell.2019.06.029

Intra- and Inter-cellular Rewiring of the Human Colon during Ulcerative Colitis

Christopher S. Smillie, Moshe Biton, Jose Ordovas-Montanes, Keri M. Sullivan, Grace Burgin, Daniel B. Graham, Rebecca H. Herbst, Noga Rogel, Michal Slyper, Julia Waldman, Malika Sud, Elizabeth Andrews, Gabriella Velonias, Adam L. Haber, Karthik Jagadeesh, Sanja Vickovic, Junmei Yao, Christine Stevens, Danielle Dionne, Lan T. NguyenAlexandra Chloé Villani, Matan Hofree, Elizabeth A. Creasey, Hailiang Huang, Orit Rozenblatt-Rosen, John J. Garber, Hamed Khalili, A. Nicole Desch, Mark J. Daly, Ashwin N. Ananthakrishnan^*, Alex K. Shalek, Ramnik J. Xavier, Aviv Regev

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

493 Scopus citations

Abstract

Single-cell analyses of colon biopsy specimens from patients with ulcerative colitis delineate how expression patterns and shifting cell populations may shape disease and drug resistance, and provide a framework for linking GWAS risk loci with specific cell types and functional pathways.

Original language	American English
Pages (from-to)	714-730.e22
Journal	Cell
Volume	178
Issue number	3
DOIs	https://doi.org/10.1016/j.cell.2019.06.029
State	Published - 25 Jul 2019
Externally published	Yes

Bibliographical note

Funding Information:
We thank all consenting participants of this study, the clinical staff at Massachusetts General Hospital, Leslie Gaffney and Anna Hupalowska for help with figures, Tim Tickle for help with the Single Cell Portal, Vijay Yajnik, Frank Colizzo, and Abdifatah Omer. M.B. was supported by a postdoctoral fellowship from the Human Frontiers Science Program . J.O.-M. is an HHMI Damon Runyon Cancer Research Foundation Fellow ( DRG-2274-16 ). Work was supported by the Klarman Cell Observatory (to A.R. and R.J.X.); HHMI (to A.R.); the Manton Foundation (to A.R. and R.X.); Broadnext10 (to A.R. and R.J.X.); DK043351 , DK114784 , DK117263 , the Helmsley Charitable Trust , and the Crohn's and Colitis Foundation (to R.J.X.); a Sloan Fellowship in Chemistry (to A.K.S.); the Searle Scholars Program (to A.K.S.); the Beckman Young Investigator Program (to A.K.S.); and NIH 5U24AI118672 (to A.R. and A.K.S.). This publication is part of the Human Cell Atlas.

Funding Information:
We thank all consenting participants of this study, the clinical staff at Massachusetts General Hospital, Leslie Gaffney and Anna Hupalowska for help with figures, Tim Tickle for help with the Single Cell Portal, Vijay Yajnik, Frank Colizzo, and Abdifatah Omer. M.B. was supported by a postdoctoral fellowship from the Human Frontiers Science Program. J.O.-M. is an HHMI Damon Runyon Cancer Research Foundation Fellow (DRG-2274-16). Work was supported by the Klarman Cell Observatory (to A.R. and R.J.X.); HHMI (to A.R.); the Manton Foundation (to A.R. and R.X.); Broadnext10 (to A.R. and R.J.X.); DK043351, DK114784, DK117263, the Helmsley Charitable Trust, and the Crohn's and Colitis Foundation (to R.J.X.); a Sloan Fellowship in Chemistry (to A.K.S.); the Searle Scholars Program (to A.K.S.); the Beckman Young Investigator Program (to A.K.S.); and NIH 5U24AI118672 (to A.R. and A.K.S.). This publication is part of the Human Cell Atlas. M.B. and J.O.-M. designed and performed experiments with A.K.S. R.J.X. A.N.A. A.R. G.B. N.R. M. Slyper, J.W. M. Sud, S.V. J.Y. E.A.C. and A.N.D. C.S.S. designed and performed computational analyses with A.R. R.J.X. D.B.G. R.H.H. A.L.H. K.J. A.-C.V. M.H. H.H. M.B. J.O.-M. and M.J.D. K.M.S. E.A. and G.V. performed clinical work with C.S. J.J.G. H.K. A.N.A. and R.J.X. D.D. L.T.N. and O.R.-R. assisted with scRNA-seq. C.S.S. M.B. J.O.-M. A.K.S. R.J.X. and A.R. wrote the manuscript with input from all authors. A.R. is an SAB member of Thermo Fisher Scientific and Syros Pharmaceuticals. A.R. and R.J.X. are cofounders of and equity holders in Celsius Therapeutics. R.J.X. is a consultant to Novartis. A.K.S is compensated for consulting and SAB membership by Honeycomb Biotechnologies, Dot Bio, Cellarity, Cogen Therapeutics, and Dahlia Biosciences. M.B. A.L.H. N.R. R.H.H. J.O.-M. O.R.-R. A.K.S. K.S. C.S.S. A.R. and R.J.X. are co-inventors on PCT/US2018/042554 relating to advances in understanding cellular dynamics, cellular effectors, and risk variants of the human colon in health and UC described in this manuscript.

Publisher Copyright:
© 2019 Elsevier Inc.

Keywords

anti-TNF resistance
cell-cell interactions
colon
genome-wide association studies
inflammation
inflammatory bowel disease
large intestine
single-cell RNA-seq
single-cell genomics
ulcerative colitis

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10.1016/j.cell.2019.06.029

Cite this

Smillie, C. S., Biton, M., Ordovas-Montanes, J., Sullivan, K. M., Burgin, G., Graham, D. B., Herbst, R. H., Rogel, N., Slyper, M., Waldman, J., Sud, M., Andrews, E., Velonias, G., Haber, A. L., Jagadeesh, K., Vickovic, S., Yao, J., Stevens, C., Dionne, D., ... Regev, A. (2019). Intra- and Inter-cellular Rewiring of the Human Colon during Ulcerative Colitis. Cell, 178(3), 714-730.e22. https://doi.org/10.1016/j.cell.2019.06.029

@article{579c8cbfcfd24ad2a3ae8edc4009c10c,

title = "Intra- and Inter-cellular Rewiring of the Human Colon during Ulcerative Colitis",

abstract = "Single-cell analyses of colon biopsy specimens from patients with ulcerative colitis delineate how expression patterns and shifting cell populations may shape disease and drug resistance, and provide a framework for linking GWAS risk loci with specific cell types and functional pathways.",

keywords = "anti-TNF resistance, cell-cell interactions, colon, genome-wide association studies, inflammation, inflammatory bowel disease, large intestine, single-cell RNA-seq, single-cell genomics, ulcerative colitis",

author = "Smillie, {Christopher S.} and Moshe Biton and Jose Ordovas-Montanes and Sullivan, {Keri M.} and Grace Burgin and Graham, {Daniel B.} and Herbst, {Rebecca H.} and Noga Rogel and Michal Slyper and Julia Waldman and Malika Sud and Elizabeth Andrews and Gabriella Velonias and Haber, {Adam L.} and Karthik Jagadeesh and Sanja Vickovic and Junmei Yao and Christine Stevens and Danielle Dionne and Nguyen, {Lan T.} and Villani, {Alexandra Chlo{\'e}} and Matan Hofree and Creasey, {Elizabeth A.} and Hailiang Huang and Orit Rozenblatt-Rosen and Garber, {John J.} and Hamed Khalili and Desch, {A. Nicole} and Daly, {Mark J.} and Ananthakrishnan, {Ashwin N.} and Shalek, {Alex K.} and Xavier, {Ramnik J.} and Aviv Regev",

note = "Funding Information: We thank all consenting participants of this study, the clinical staff at Massachusetts General Hospital, Leslie Gaffney and Anna Hupalowska for help with figures, Tim Tickle for help with the Single Cell Portal, Vijay Yajnik, Frank Colizzo, and Abdifatah Omer. M.B. was supported by a postdoctoral fellowship from the Human Frontiers Science Program . J.O.-M. is an HHMI Damon Runyon Cancer Research Foundation Fellow ( DRG-2274-16 ). Work was supported by the Klarman Cell Observatory (to A.R. and R.J.X.); HHMI (to A.R.); the Manton Foundation (to A.R. and R.X.); Broadnext10 (to A.R. and R.J.X.); DK043351 , DK114784 , DK117263 , the Helmsley Charitable Trust , and the Crohn's and Colitis Foundation (to R.J.X.); a Sloan Fellowship in Chemistry (to A.K.S.); the Searle Scholars Program (to A.K.S.); the Beckman Young Investigator Program (to A.K.S.); and NIH 5U24AI118672 (to A.R. and A.K.S.). This publication is part of the Human Cell Atlas. Funding Information: We thank all consenting participants of this study, the clinical staff at Massachusetts General Hospital, Leslie Gaffney and Anna Hupalowska for help with figures, Tim Tickle for help with the Single Cell Portal, Vijay Yajnik, Frank Colizzo, and Abdifatah Omer. M.B. was supported by a postdoctoral fellowship from the Human Frontiers Science Program. J.O.-M. is an HHMI Damon Runyon Cancer Research Foundation Fellow (DRG-2274-16). Work was supported by the Klarman Cell Observatory (to A.R. and R.J.X.); HHMI (to A.R.); the Manton Foundation (to A.R. and R.X.); Broadnext10 (to A.R. and R.J.X.); DK043351, DK114784, DK117263, the Helmsley Charitable Trust, and the Crohn's and Colitis Foundation (to R.J.X.); a Sloan Fellowship in Chemistry (to A.K.S.); the Searle Scholars Program (to A.K.S.); the Beckman Young Investigator Program (to A.K.S.); and NIH 5U24AI118672 (to A.R. and A.K.S.). This publication is part of the Human Cell Atlas. M.B. and J.O.-M. designed and performed experiments with A.K.S. R.J.X. A.N.A. A.R. G.B. N.R. M. Slyper, J.W. M. Sud, S.V. J.Y. E.A.C. and A.N.D. C.S.S. designed and performed computational analyses with A.R. R.J.X. D.B.G. R.H.H. A.L.H. K.J. A.-C.V. M.H. H.H. M.B. J.O.-M. and M.J.D. K.M.S. E.A. and G.V. performed clinical work with C.S. J.J.G. H.K. A.N.A. and R.J.X. D.D. L.T.N. and O.R.-R. assisted with scRNA-seq. C.S.S. M.B. J.O.-M. A.K.S. R.J.X. and A.R. wrote the manuscript with input from all authors. A.R. is an SAB member of Thermo Fisher Scientific and Syros Pharmaceuticals. A.R. and R.J.X. are cofounders of and equity holders in Celsius Therapeutics. R.J.X. is a consultant to Novartis. A.K.S is compensated for consulting and SAB membership by Honeycomb Biotechnologies, Dot Bio, Cellarity, Cogen Therapeutics, and Dahlia Biosciences. M.B. A.L.H. N.R. R.H.H. J.O.-M. O.R.-R. A.K.S. K.S. C.S.S. A.R. and R.J.X. are co-inventors on PCT/US2018/042554 relating to advances in understanding cellular dynamics, cellular effectors, and risk variants of the human colon in health and UC described in this manuscript. Publisher Copyright: {\textcopyright} 2019 Elsevier Inc.",

year = "2019",

month = jul,

day = "25",

doi = "10.1016/j.cell.2019.06.029",

language = "American English",

volume = "178",

pages = "714--730.e22",

journal = "Cell",

issn = "0092-8674",

publisher = "Cell Press",

number = "3",

}

Smillie, CS, Biton, M, Ordovas-Montanes, J, Sullivan, KM, Burgin, G, Graham, DB, Herbst, RH, Rogel, N, Slyper, M, Waldman, J, Sud, M, Andrews, E, Velonias, G, Haber, AL, Jagadeesh, K, Vickovic, S, Yao, J, Stevens, C, Dionne, D, Nguyen, LT, Villani, AC, Hofree, M, Creasey, EA, Huang, H, Rozenblatt-Rosen, O, Garber, JJ, Khalili, H, Desch, AN, Daly, MJ, Ananthakrishnan, AN, Shalek, AK, Xavier, RJ & Regev, A 2019, 'Intra- and Inter-cellular Rewiring of the Human Colon during Ulcerative Colitis', Cell, vol. 178, no. 3, pp. 714-730.e22. https://doi.org/10.1016/j.cell.2019.06.029

TY - JOUR

T1 - Intra- and Inter-cellular Rewiring of the Human Colon during Ulcerative Colitis

AU - Smillie, Christopher S.

AU - Biton, Moshe

AU - Ordovas-Montanes, Jose

AU - Sullivan, Keri M.

AU - Burgin, Grace

AU - Graham, Daniel B.

AU - Herbst, Rebecca H.

AU - Rogel, Noga

AU - Slyper, Michal

AU - Waldman, Julia

AU - Sud, Malika

AU - Andrews, Elizabeth

AU - Velonias, Gabriella

AU - Haber, Adam L.

AU - Jagadeesh, Karthik

AU - Vickovic, Sanja

AU - Yao, Junmei

AU - Stevens, Christine

AU - Dionne, Danielle

AU - Nguyen, Lan T.

AU - Villani, Alexandra Chloé

AU - Hofree, Matan

AU - Creasey, Elizabeth A.

AU - Huang, Hailiang

AU - Rozenblatt-Rosen, Orit

AU - Garber, John J.

AU - Khalili, Hamed

AU - Desch, A. Nicole

AU - Daly, Mark J.

AU - Ananthakrishnan, Ashwin N.

AU - Shalek, Alex K.

AU - Xavier, Ramnik J.

AU - Regev, Aviv

N1 - Funding Information: We thank all consenting participants of this study, the clinical staff at Massachusetts General Hospital, Leslie Gaffney and Anna Hupalowska for help with figures, Tim Tickle for help with the Single Cell Portal, Vijay Yajnik, Frank Colizzo, and Abdifatah Omer. M.B. was supported by a postdoctoral fellowship from the Human Frontiers Science Program . J.O.-M. is an HHMI Damon Runyon Cancer Research Foundation Fellow ( DRG-2274-16 ). Work was supported by the Klarman Cell Observatory (to A.R. and R.J.X.); HHMI (to A.R.); the Manton Foundation (to A.R. and R.X.); Broadnext10 (to A.R. and R.J.X.); DK043351 , DK114784 , DK117263 , the Helmsley Charitable Trust , and the Crohn's and Colitis Foundation (to R.J.X.); a Sloan Fellowship in Chemistry (to A.K.S.); the Searle Scholars Program (to A.K.S.); the Beckman Young Investigator Program (to A.K.S.); and NIH 5U24AI118672 (to A.R. and A.K.S.). This publication is part of the Human Cell Atlas. Funding Information: We thank all consenting participants of this study, the clinical staff at Massachusetts General Hospital, Leslie Gaffney and Anna Hupalowska for help with figures, Tim Tickle for help with the Single Cell Portal, Vijay Yajnik, Frank Colizzo, and Abdifatah Omer. M.B. was supported by a postdoctoral fellowship from the Human Frontiers Science Program. J.O.-M. is an HHMI Damon Runyon Cancer Research Foundation Fellow (DRG-2274-16). Work was supported by the Klarman Cell Observatory (to A.R. and R.J.X.); HHMI (to A.R.); the Manton Foundation (to A.R. and R.X.); Broadnext10 (to A.R. and R.J.X.); DK043351, DK114784, DK117263, the Helmsley Charitable Trust, and the Crohn's and Colitis Foundation (to R.J.X.); a Sloan Fellowship in Chemistry (to A.K.S.); the Searle Scholars Program (to A.K.S.); the Beckman Young Investigator Program (to A.K.S.); and NIH 5U24AI118672 (to A.R. and A.K.S.). This publication is part of the Human Cell Atlas. M.B. and J.O.-M. designed and performed experiments with A.K.S. R.J.X. A.N.A. A.R. G.B. N.R. M. Slyper, J.W. M. Sud, S.V. J.Y. E.A.C. and A.N.D. C.S.S. designed and performed computational analyses with A.R. R.J.X. D.B.G. R.H.H. A.L.H. K.J. A.-C.V. M.H. H.H. M.B. J.O.-M. and M.J.D. K.M.S. E.A. and G.V. performed clinical work with C.S. J.J.G. H.K. A.N.A. and R.J.X. D.D. L.T.N. and O.R.-R. assisted with scRNA-seq. C.S.S. M.B. J.O.-M. A.K.S. R.J.X. and A.R. wrote the manuscript with input from all authors. A.R. is an SAB member of Thermo Fisher Scientific and Syros Pharmaceuticals. A.R. and R.J.X. are cofounders of and equity holders in Celsius Therapeutics. R.J.X. is a consultant to Novartis. A.K.S is compensated for consulting and SAB membership by Honeycomb Biotechnologies, Dot Bio, Cellarity, Cogen Therapeutics, and Dahlia Biosciences. M.B. A.L.H. N.R. R.H.H. J.O.-M. O.R.-R. A.K.S. K.S. C.S.S. A.R. and R.J.X. are co-inventors on PCT/US2018/042554 relating to advances in understanding cellular dynamics, cellular effectors, and risk variants of the human colon in health and UC described in this manuscript. Publisher Copyright: © 2019 Elsevier Inc.

PY - 2019/7/25

Y1 - 2019/7/25

N2 - Single-cell analyses of colon biopsy specimens from patients with ulcerative colitis delineate how expression patterns and shifting cell populations may shape disease and drug resistance, and provide a framework for linking GWAS risk loci with specific cell types and functional pathways.

AB - Single-cell analyses of colon biopsy specimens from patients with ulcerative colitis delineate how expression patterns and shifting cell populations may shape disease and drug resistance, and provide a framework for linking GWAS risk loci with specific cell types and functional pathways.

KW - anti-TNF resistance

KW - cell-cell interactions

KW - colon

KW - genome-wide association studies

KW - inflammation

KW - inflammatory bowel disease

KW - large intestine

KW - single-cell RNA-seq

KW - single-cell genomics

KW - ulcerative colitis

UR - http://www.scopus.com/inward/record.url?scp=85069176109&partnerID=8YFLogxK

U2 - 10.1016/j.cell.2019.06.029

DO - 10.1016/j.cell.2019.06.029

M3 - Article

C2 - 31348891

AN - SCOPUS:85069176109

SN - 0092-8674

VL - 178

SP - 714-730.e22

JO - Cell

JF - Cell

IS - 3

ER -

Intra- and Inter-cellular Rewiring of the Human Colon during Ulcerative Colitis

Abstract

Bibliographical note

Keywords

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