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| Status |
Public on Aug 29, 2019 |
| Title |
Single-cell analysis of Crohn’s disease lesions identifies a pathogenic cellular module associated with resistance to anti-TNF therapy |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Clinical benefits of cytokine blockade in ileal Crohn’s disease (iCD) are limited to a subset of patients. Here we applied single cell technologies to iCD lesions to address whether cellular heterogeneity contributes to treatment resistance. We found that a subset of patients expressed a unique cellular module in inflamed tissues that consisted of IgG plasma cells, inflammatory mononuclear phagocytes, activated T cells and stromal cells, which we named the GIMATS module. Analysis of ligand-receptor interaction pairs identified a distinct connectivity network that likely drives the GIMATS module. Strikingly, the GIMATS module was also present in a subset of patients in 4 independent iCD cohorts (n=441), and its presence at diagnosis correlated with failure to achieve corticosteroid-free durable remission upon anti-TNF therapy. These results emphasize the limitations of current diagnostic assays and the potential for single cell mapping tools to identify novel biomarkers of treatment response and tailored therapeutic opportunities
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| Overall design |
Single cell seq analysis of paired resection ileal samples from inflamed and uninflamed area
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| Contributor(s) |
Cho J, Martin J, Merad M, Kenigsberg E, Giri M |
| Citation(s) |
31474370, 37080976 |
| NIH grant(s) |
| Grant ID |
Grant title |
Affiliation |
Name |
| U24 DK062429 |
Inflammatory Bowel Disease Genetics Consortium Data Coordinating Center |
MOUNT SINAI SCHOOL OF MEDICINE |
JUDY H. CHO |
| U01 DK062422 |
Mount Sinai School of Medicine Inflammatory Bowel Disease Genetics Research Cente |
MOUNT SINAI SCHOOL OF MEDICINE |
JUDY H. CHO |
| R01 DK106593 |
Integrative Genomic Analyses of Macrophages in Crohns Disease |
MOUNT SINAI SCHOOL OF MEDICINE |
JUDY H. CHO |
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| |
| Submission date |
Jul 24, 2019 |
| Last update date |
May 12, 2023 |
| Contact name |
Mamta Giri |
| E-mail(s) |
mamta.giri@mssm.edu
|
| Organization name |
Mount Sinai hospital
|
| Department |
Institute of Personalized medicine
|
| Lab |
Cho lab
|
| Street address |
1470 madison ave
|
| City |
new york |
| State/province |
new york |
| ZIP/Postal code |
10029 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
|
| Samples (31)
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| Relations |
| BioProject |
PRJNA556461 |
| SRA |
SRP216273 |
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