التفاصيل البيبلوغرافية
| العنوان: |
Single-cell RNA sequencing reveals dysregulated cellular programs in the inflamed epithelium of Crohn's disease patients. |
| المؤلفون: |
Krzak Monika, Alegbe Tobi, Taylor Leland D, Ghouraba H Mennatallah, Strickland Michelle, Satti Reem, Thompson Tina, Arestang Kenneth, Przybilla J Moritz, Ramirez-Navarro Lucia, Harris T Bradley, Cheam Ai Xian Kimberley, Noell Guillaume, Leonard Steven, Petrova Velislava, Jones-Bell Carla, James R Kylie, Wana Noor, Hu Xueqi May, Skelton Jason, Ostermayer Jasmin, Gu Yong, Dawson Claire, Corridoni Daniele, Martin Cotobal Cristina, Parkes Miles, Iyer Vivek, Rhys-Jones Gareth, McIntyre E Rebecca, Raine Tim, Anderson A Carl |
| بيانات النشر: |
Zenodo |
| سنة النشر: |
2023 |
| المجموعة: |
Zenodo |
| مصطلحات موضوعية: |
IBD, Crohn's disease, scRNAseq |
| الوصف: |
Crohn’s disease (CD) is a complex inflammatory disorder of incompletely understood molecular aetiology. We generated a large single-cell RNA sequencing dataset from the terminal ileal biopsies of two independent cohorts comprising a total of 50 CD patients and 71 healthy controls. We performed transcriptomic analyses to reveal genes, cell types and mechanisms perturbed in CD, leveraging the power of the two cohorts to confirm our findings and assess replicability. In addition to mapping widespread alterations in cytokine signalling, we provide evidence of pan-epithelial upregulation of MHC class I genes and pathways in CD. Using non-negative matrix factorization we revealed intra- and inter-cellular upregulation of expression programs such as G-protein coupled receptor signalling and interferon signalling, respectively, in CD. We observed an enrichment of CD heritability among marker genes for various activated T cell types and myeloid cells, supporting a causal role for these cell-types in CD aetiology. Comparisons between our discovery and replication cohort revealed significant variation in differential gene-expression replicability across cell types. B, T and myeloid cells showed particularly poor replicability, suggesting caution should be exercised when interpreting unreplicated differential gene-expression result in these cell types. Overall, our results provide a rich resource for identifying cell-type specific biomarkers of Crohn’s disease and identifying genes, cell types and pathways that are causally and replicably associated with disease. |
| نوع الوثيقة: |
other/unknown material |
| اللغة: |
English |
| Relation: |
https://doi.org/10.5281/zenodo.8301000; https://doi.org/10.5281/zenodo.10528153; oai:zenodo.org:10528153 |
| DOI: |
10.5281/zenodo.10528153 |
| الاتاحة: |
https://doi.org/10.5281/zenodo.10528153 |
| Rights: |
info:eu-repo/semantics/openAccess ; Creative Commons Attribution 4.0 International ; https://creativecommons.org/licenses/by/4.0/legalcode |
| رقم الانضمام: |
edsbas.5FD9AAA0 |
| قاعدة البيانات: |
BASE |