HCA Data Explorer

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

Updated August 30, 2022

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<sup>+</sup> enterocytes, microfold-like cells, and IL13RA2<sup>+</sup>IL11<sup>+</sup> 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 co-regulated 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.

Ashwin N AnanthakrishnanGastrointestinal Unit and Center for the Study of Inflammatory Bowel Disease, MGH, Boston, MA, USAaananthakrishnan@mgh.harvard.edu
Alex K ShalekKlarman Cell Observatory, Broad Institute, Cambridge, MA, USAshalek@mit.edu
Ramnik J XavierDepartment of Molecular Biology, MGH, Boston, MA, USAxavier@molbio.mgh.harvard.edu
Aviv RegevBroad Institutearegev@broadinstitute.org
Christopher S Smillie1
Moshe Biton1
Jose Ordovas-Montanes1
Keri M Sullivan2
Grace Burgin1
Daniel B Graham3
Rebecca H Herbst4
Noga Rogel5
Michal Slyper5
Julia Waldman5
Malika Sud5
Elizabeth Andrews6
Gabriella Velonias6
Adam L Haber5
Karthik Jagadeesh5
Sanja Vickovic5
Junmei Yao7
Christine Stevens8
Danielle Dionne5
Lan T Nguyen5
Alexandra-Chloé Villani4
Matan Hofree5
Elizabeth A Creasey7
Hailiang Huang9
Orit Rozenblatt-Rosen5
John J Garber6
Hamed Khalili6
A Nicole Desch10
Mark J Daly9
Ashwin N Ananthakrishnan11
Alex K Shalek4
Ramnik J Xavier3
Aviv Regev1
1Broad Institute
2Massachusetts General Hospital
3Department of Molecular Biology, MGH, Boston, MA, USA
4Klarman Cell Observatory, Broad Institute, Cambridge, MA, USA
5Klarman Cell Observatory, Broad Institute, Cambridge, MA, USA.
6Gastrointestinal Unit and Center for the Study of Inflammatory Bowel Disease, MGH, Boston, MA, USA.
7Center for Computational and Integrative Biology, MGH, Boston, MA, USA.
8Broad Institute, Cambridge, MA, USA.
9Medical and Population Genetics, Broad Institute, Cambridge, MA, USA
10Broad Institute, Cambridge, MA, USA
11Gastrointestinal Unit and Center for the Study of Inflammatory Bowel Disease, MGH, Boston, MA, USA
Irene Pérez-Díez

To reference this project, please use the following link:

https://explore.data.humancellatlas.org/projects/cd61771b-661a-4e19-b269-6e5d95350de6

Supplementary links are provided by contributors and represent items such as additional data which can’t be hosted here; code that was used to analyze this data; or tools and visualizations associated with this specific dataset.

1.https://github.com/cssmillie/ulcerative_colitis2.https://singlecell.broadinstitute.org/single_cell/study/SCP259
None

For information regarding data sharing and data use, please see our Data Access Policy.

Analysis Portals

CZ CELLxGENECZ CELLxGENE
UCSC Cell BrowserUCSC Cell Browser

Project Label

HumanColonRewiringUlcerativeColitis

Species

Homo sapiens

Sample Type

specimens

Anatomical Entity

7 anatomical entities

Organ Part

8 organ parts

Selected Cell Types

Unspecified

Disease Status (Specimen)

2 disease statuses

Disease Status (Donor)

2 disease statuses

Development Stage

human adult stage

Library Construction Method

2 library construction methods

Nucleic Acid Source

single cell

Paired End

false

Analysis Protocol

PCA_protocol, batch_correction_protocol, count_matrix_protocol, normalization_protocol, tSNE_protocol

File Format

5 file formats

Cell Count Estimate

366.6k

Donor Count

30
mtx3 file(s)rds3 file(s)tsv6 file(s)txt1 file(s)xlsx1 file(s)