Single-Cell Analyses Elucidate the Cellular and Molecular Landscape of Ulcerative Colitis

Dataset overview

Participants 16

Samples None

Reuse readiness 6.3/10 evidence-backed score

Heterogeneity and clonal relationships of adaptive immune cells in ulcerative colitis revealed by single-cell analyses.

Boland BS, He Z, Tsai MS, Olvera JG, Omilusik KD, Duong HG, Kim ES, Limary AE, et al. · Science immunology · 2020

Abstract

Inflammatory bowel disease (IBD) encompasses a spectrum of gastrointestinal disorders driven by dysregulated immune responses against gut microbiota. We integrated single-cell RNA and antigen receptor sequencing to elucidate key components, cellular states, and clonal relationships of the peripheral and gastrointestinal mucosal immune systems in health and ulcerative colitis (UC). UC was associated with an increase in IgG1+ plasma cells in colonic tissue, increased colonic regulatory T cells characterized by elevated expression of the transcription factor ZEB2, and an enrichment of a γδ T cell subset in the peripheral blood. Moreover, we observed heterogeneity in CD8+ tissue-resident memory T (TRM) cells in colonic tissue, with four transcriptionally distinct states of differentiation observed across health and disease. In the setting of UC, there was a marked shift of clonally related CD8+ TRM cells toward an inflammatory state, mediated, in part, by increased expression of the T-box transcription factor Eomesodermin. Together, these results provide a detailed atlas of transcriptional changes occurring in adaptive immune cells in the context of UC and suggest a role for CD8+ TRM cells in IBD.

doi:10.1126/sciimmunol.abb4432 ↗ PMID 32826341 ↗ PMC7733868 ↗

Study facts

Organism: Homo sapiens
Platform: 10X Genomics
Age group: —
Disease groups: —
Anatomical sites: rectum, ileum, peripheral blood

Data availability

Raw counts
Processed matrix

File types CSVTSV

rectum44
PBMC43
ileum16

Accession	Sample	Tissue	Molecule
`GSM3576396`	C9_R_10x_scRNA	rectum	total RNA
`GSM3576397`	C12_R_10x_scRNA	rectum	total RNA
`GSM3576398`	C16_R_10x_scRNA	rectum	total RNA
`GSM3576399`	U4_R_10x_scRNA	rectum	total RNA
`GSM3576400`	U5_R_10x_scRNA	rectum	total RNA
`GSM3576401`	U34_R_10x_scRNA	rectum	total RNA
`GSM3576402`	U35_R_10x_scRNA	rectum	total RNA
`GSM3576403`	U41_R_10x_scRNA	rectum	total RNA
`GSM3576404`	U44_R_10x_scRNA	rectum	total RNA
`GSM3576405`	U45_R_10x_scRNA	rectum	total RNA
`GSM3576406`	C17_R_10x_scRNA	rectum	total RNA
`GSM3576407`	C18_R_10x_scRNA	rectum	total RNA
`GSM3576408`	C19_R_10x_scRNA	rectum	total RNA
`GSM3576409`	C21_R_10x_scRNA	rectum	total RNA
`GSM3576410`	C30_R_10x_scRNA	rectum	total RNA
`GSM3576411`	C12_PBMC_10x_scRNA	PBMC	total RNA
`GSM3576412`	C16_PBMC_10x_scRNA	PBMC	total RNA
`GSM3576413`	U4_PBMC_10x_scRNA	PBMC	total RNA
`GSM3576414`	U5_PBMC_10x_scRNA	PBMC	total RNA
`GSM3576415`	U34_PBMC_10x_scRNA	PBMC	total RNA
`GSM3576416`	U35_PBMC_10x_scRNA	PBMC	total RNA
`GSM3576417`	U41_PBMC_10x_scRNA	PBMC	total RNA
`GSM3576418`	U44_PBMC_10x_scRNA	PBMC	total RNA
`GSM3576419`	U45_PBMC_10x_scRNA	PBMC	total RNA
`GSM3576420`	C17_PBMC_10x_scRNA	PBMC	total RNA
`GSM3576421`	C18_PBMC_10x_scRNA	PBMC	total RNA
`GSM3576422`	C19_PBMC_10x_scRNA	PBMC	total RNA
`GSM3576423`	C21_PBMC_10x_scRNA	PBMC	total RNA
`GSM3576424`	C30_PBMC_10x_scRNA	PBMC	total RNA
`GSM3576425`	C33_PBMC_10x_scRNA	PBMC	total RNA
`GSM3576426`	C17_I_10x_scRNA	ileum	total RNA
`GSM3576427`	C18_I_10x_scRNA	ileum	total RNA
`GSM3576428`	C19_I_10x_scRNA	ileum	total RNA
`GSM3576429`	C21_I_10x_scRNA	ileum	total RNA
`GSM3576430`	C30_I_10x_scRNA	ileum	total RNA
`GSM3576431`	C33_I_10x_scRNA	ileum	total RNA
`GSM3576432`	C9_R_10x_BCR	rectum	total RNA
`GSM3576433`	C12_R_10x_BCR	rectum	total RNA
`GSM3576434`	C16_R_10x_BCR	rectum	total RNA
`GSM3576435`	U4_R_10x_BCR	rectum	total RNA
`GSM3576436`	U5_R_10x_BCR	rectum	total RNA
`GSM3576437`	U34_R_10x_BCR	rectum	total RNA
`GSM3576438`	U35_R_10x_BCR	rectum	total RNA
`GSM3576439`	U41_R_10x_BCR	rectum	total RNA
`GSM3576440`	U45_R_10x_BCR	rectum	total RNA
`GSM3576441`	C17_R_10x_BCR	rectum	total RNA
`GSM3576442`	C18_R_10x_BCR	rectum	total RNA
`GSM3576443`	C19_R_10x_BCR	rectum	total RNA
`GSM3576444`	C21_R_10x_BCR	rectum	total RNA
`GSM3576445`	C30_R_10x_BCR	rectum	total RNA
`GSM3576446`	C12_PBMC_10x_BCR	PBMC	total RNA
`GSM3576447`	C16_PBMC_10x_BCR	PBMC	total RNA
`GSM3576448`	U4_PBMC_10x_BCR	PBMC	total RNA
`GSM3576449`	U5_PBMC_10x_BCR	PBMC	total RNA
`GSM3576450`	U34_PBMC_10x_BCR	PBMC	total RNA
`GSM3576451`	U35_PBMC_10x_BCR	PBMC	total RNA
`GSM3576452`	U41_PBMC_10x_BCR	PBMC	total RNA
`GSM3576453`	U44_PBMC_10x_BCR	PBMC	total RNA
`GSM3576454`	U45_PBMC_10x_BCR	PBMC	total RNA
`GSM3576455`	C17_PBMC_10x_BCR	PBMC	total RNA
`GSM3576456`	C18_PBMC_10x_BCR	PBMC	total RNA
`GSM3576457`	C21_PBMC_10x_BCR	PBMC	total RNA
`GSM3576458`	C30_PBMC_10x_BCR	PBMC	total RNA
`GSM3576459`	C33_PBMC_10x_BCR	PBMC	total RNA
`GSM3576460`	C17_I_10x_BCR	ileum	total RNA
`GSM3576461`	C18_I_10x_BCR	ileum	total RNA
`GSM3576462`	C21_I_10x_BCR	ileum	total RNA
`GSM3576463`	C30_I_10x_BCR	ileum	total RNA
`GSM3576464`	C33_I_10x_BCR	ileum	total RNA
`GSM3576465`	C9_R_10x_TCR	rectum	total RNA
`GSM3576466`	C12_R_10x_TCR	rectum	total RNA
`GSM3576467`	C16_R_10x_TCR	rectum	total RNA
`GSM3576468`	U4_R_10x_TCR	rectum	total RNA
`GSM3576469`	U5_R_10x_TCR	rectum	total RNA
`GSM3576470`	U34_R_10x_TCR	rectum	total RNA
`GSM3576471`	U35_R_10x_TCR	rectum	total RNA
`GSM3576472`	U41_R_10x_TCR	rectum	total RNA
`GSM3576473`	U44_R_10x_TCR	rectum	total RNA
`GSM3576474`	U45_R_10x_TCR	rectum	total RNA
`GSM3576475`	C17_R_10x_TCR	rectum	total RNA
`GSM3576476`	C18_R_10x_TCR	rectum	total RNA
`GSM3576477`	C19_R_10x_TCR	rectum	total RNA
`GSM3576478`	C21_R_10x_TCR	rectum	total RNA
`GSM3576479`	C30_R_10x_TCR	rectum	total RNA
`GSM3576480`	C12_PBMC_10x_TCR	PBMC	total RNA
`GSM3576481`	C16_PBMC_10x_TCR	PBMC	total RNA
`GSM3576482`	U4_PBMC_10x_TCR	PBMC	total RNA
`GSM3576483`	U5_PBMC_10x_TCR	PBMC	total RNA
`GSM3576484`	U34_PBMC_10x_TCR	PBMC	total RNA
`GSM3576485`	U35_PBMC_10x_TCR	PBMC	total RNA
`GSM3576486`	U41_PBMC_10x_TCR	PBMC	total RNA
`GSM3576487`	U44_PBMC_10x_TCR	PBMC	total RNA
`GSM3576488`	U45_PBMC_10x_TCR	PBMC	total RNA
`GSM3576489`	C17_PBMC_10x_TCR	PBMC	total RNA
`GSM3576490`	C18_PBMC_10x_TCR	PBMC	total RNA
`GSM3576491`	C21_PBMC_10x_TCR	PBMC	total RNA
`GSM3576492`	C30_PBMC_10x_TCR	PBMC	total RNA
`GSM3576493`	C33_PBMC_10x_TCR	PBMC	total RNA
`GSM3576494`	C17_I_10x_TCR	ileum	total RNA
`GSM3576495`	C18_I_10x_TCR	ileum	total RNA
`GSM3576496`	C21_I_10x_TCR	ileum	total RNA
`GSM3576497`	C30_I_10x_TCR	ileum	total RNA
`GSM3576498`	C33_I_10x_TCR	ileum	total RNA

Strengths & limitations for reuse

Strengths

Raw reads are advertised
Raw counts are advertised
Processed matrices are advertised
Cell metadata are advertised
Participant mapping is available
Participant counts are documented

Extraction evidence & provenance

Each extracted field is shown with the source excerpt and location used to resolve it.

Assay

Field	Value	Evidence
`assay.assay_type`	single-cell RNA-seq	Single-cell RNA-seq and BCR/TCR repertoire analyses of immune cell from 15 patients Section `series.series_overall_design`, offset —
`assay.library_chemistry`	10X Genomics Single Cell V(D)J + 5’ Gene Expression	Single cell libraries were prepared according to the protocol for 10X Genomics for Single Cell V(D)J + 5’ Gene Expression. Section `samples.extract_protocol`, offset —
`assay.platform`	10X Genomics	Single cell libraries were prepared according to the protocol for 10X Genomics for Single Cell V(D)J + 5’ Gene Expression. Section `samples.extract_protocol`, offset —
`assay.reference_genome`	hg38	Genome_build: hg38 Section `samples.data_processing`, offset —
`assay.sequencing_type`	scrna_seq	We generated an integrated single-cell (scRNA-seq, scTCR-seq, and scBCR-seq) resource dataset Section `series`, offset —

Cohort

Field Value Evidence

Field	Value	Evidence
`cohort.total_participants`	16 computed	16 distinct subject/participant IDs across GEO samples Section `GEO family SOFT`, offset —

cohort.total_participants

16 computed

16 distinct subject/participant IDs across GEO samples

Section GEO family SOFT, offset —

Data_Assets

Field	Value	Evidence
`data_assets.cell_metadata`	True	GSE125527_cell_metadata.csv.gz Section `geo_document`, offset —
`data_assets.open_access`	True	Public on Jul 16 2020 Section `series`, offset —
`data_assets.participant_metadata`	True	GSE125527_oldPatientId-newPatientId.csv.gz Section `geo_document`, offset —
`data_assets.processed_matrix`	True	GSE125527_UMI_cell_table_sparse.csv.gz Section `geo_document`, offset —
`data_assets.raw_counts`	True	GSE125527_UMI_cell_table_sparse.csv.gz Section `geo_document`, offset —
`data_assets.raw_reads`	True	GSE125527_RAW.tar Section `geo_document`, offset —

Processing

Field Value Evidence

Field	Value	Evidence
`processing.quality_control_reported`	True	Only cells with > 400 genes,UMI > 0,and 0.5% ~ 30% of their UMIs mappingto mitochondria genes were kept for downstream analysis. Section `samples`, offset —

processing.quality_control_reported

True

Only cells with > 400 genes,UMI > 0,and 0.5% ~ 30% of their UMIs mappingto mitochondria genes were kept for downstream analysis.

Section samples, offset —

Specimens

Field Value Evidence

Field	Value	Evidence
`specimens.anatomical_sites`	['rectum', 'ileum', 'peripheral blood']	source_name": "Rectum immune cell" Section `samples`, offset —
`specimens.participant_to_sample_mapping_available`	True	"subject #": "C9" Section `samples`, offset —
`specimens.specimen_type`	biopsy	Four intestinal biopsies were obtained with endoscopic biopsy forceps from the rectum or ileum Section `samples.extract_protocol`, offset —

specimens.anatomical_sites

['rectum', 'ileum', 'peripheral blood']

source_name": "Rectum immune cell"

Section samples, offset —

specimens.participant_to_sample_mapping_available

True

"subject #": "C9"

Section samples, offset —

specimens.specimen_type

biopsy

Four intestinal biopsies were obtained with endoscopic biopsy forceps from the rectum or ileum

Section samples.extract_protocol, offset —

Dataset overview

Study facts

Data availability

Files and samples

Strengths & limitations for reuse

Strengths

Assay

Cohort

Data_Assets

Processing

Specimens