التفاصيل البيبلوغرافية
| العنوان: |
Intra- and Inter-cellular Rewiring of the Human Colon during Ulcerative Colitis |
| المؤلفون: |
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 |
| المساهمون: |
Institute for Molecular Medicine Finland, University of Helsinki |
| بيانات النشر: |
Cell Press |
| سنة النشر: |
2020 |
| المجموعة: |
Helsingfors Universitet: HELDA – Helsingin yliopiston digitaalinen arkisto |
| مصطلحات موضوعية: |
INFLAMMATORY-BOWEL-DISEASE, GENE-EXPRESSION, RNA-SEQ, DENDRITIC CELLS, T-CELLS, DATABASE, LOCI, DIFFERENTIATION, ASSOCIATION, ANTIBODIES, 1182 Biochemistry, cell and molecular biology |
| الوصف: |
Genome-wide association studies (GWAS) have revealed risk alleles for ulcerative colitis (UC). To understand their cell type specificities and pathways of action, we generate an atlas of 366,650 cells from the colon mucosa of 18 UC patients and 12 healthy individuals, revealing 51 epithelial, stromal, and immune cell subsets, including BEST4(+) enterocytes, microfold-like cells, and IL13RA2(+)IL11(+) inflammatory fibroblasts, which we associate with resistance to anti-TNF treatment. Inflammatory fibroblasts, inflammatory monocytes, microfold-like cells, and T cells that co-express CD8 and IL-17 expand with disease, forming intercellular interaction hubs. Many UC risk genes are cell type specific and coregulated within relatively few gene modules, suggesting convergence onto limited sets of cell types and pathways. Using this observation, we nominate and infer functions for specific risk genes across GWAS loci. Our work provides a framework for interrogating complex human diseases and mapping risk variants to cell types and pathways. ; Peer reviewed |
| نوع الوثيقة: |
article in journal/newspaper |
| وصف الملف: |
application/pdf |
| اللغة: |
English |
| العلاقة: |
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.; 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 , Nguyen , L T , Villani , A-C , Hofree , M , Creasey , E A , Huang , H , Rozenblatt-Rosen , O , Garber , J J , Khalili , H , Desch , A N , Daly , M J , Ananthakrishnan , A N , Shalek , A K , Xavier , R J & Regev , A 2019 , ' Intra- and Inter-cellular Rewiring of the Human Colon during Ulcerative Colitis ' , Cell , vol. 178 , no. 3 , pp. 714-+ . https://doi.org/10.1016/j.cell.2019.06.029Test; 1f0997a2-58bd-4e9e-a0a6-a7cf896aaf82; http://hdl.handle.net/10138/320937Test; 000476973800018 |
| الإتاحة: |
http://hdl.handle.net/10138/320937Test |
| حقوق: |
openAccess ; info:eu-repo/semantics/openAccess |
| رقم الانضمام: |
edsbas.2C24718C |
| قاعدة البيانات: |
BASE |
