Single-cell RNA sequencing unifies developmental programs of Esophageal and Gastric Intestinal Metaplasia
Karol Nowicki-Osuch, Lizhe Zhuang, Tik Shing Cheung, Emily L. Black, Neus Masqué-Soler, Ginny Devonshire, Aisling M. Redmond, Adam Freeman, Massimilliano di Pietro, Nastazja Pilonis, Wladyslaw Januszewicz, Maria O'Donovan, Simon Tavaré, Jacqueline D. Shields, Rebecca C. Fitzgerald
Abstract
Intestinal metaplasia in the esophagus (Barrett's esophagus IM, or BE-IM) and stomach (GIM) are considered precursors for esophageal and gastric adenocarcinoma, respectively. We hypothesize that BE-IM and GIM follow parallel developmental trajectories in response to differing inflammatory insults. Here, we construct a single-cell RNA-sequencing atlas, supported by protein expression studies, of the entire gastrointestinal tract spanning physiologically normal and pathologic states including gastric metaplasia in the esophagus (E-GM), BE-IM, atrophic gastritis, and GIM. We demonstrate that BE-IM and GIM share molecular features, and individual cells simultaneously possess transcriptional properties of gastric and intestinal epithelia, suggesting phenotypic mosaicism. Transcriptionally E-GM resembles atrophic gastritis; genetically, it is clonal and has a lower mutational burden than BE-IM. Finally, we show that GIM and BE-IM acquire a protumorigenic, activated fibroblast microenvironment. These findings suggest that BE-IM and GIM can be considered molecularly similar entities in adjacent organs, opening the path for shared detection and treatment strategies.
Datasets
1. UMAP of Cancer Data integration
Metadata
Tissue_in_paper
Batch
Sample_Barcode
Study
Patient_type
Patient_status
Global_cluster_selected
Celltypes_global
Tissuetypes_global
Detailed_Cell_Type
cell_type_ontology_term_id
assay_ontology_term_id
tissue_ontology_term_id
disease_ontology_term_id
sex_ontology_term_id
organism_ontology_term_id
self_reported_ethnicity_ontology_term_id
donor_id
Cancer_type
Stage
Location
IM.Status
MMR_Status
Global_cluster
suspension_type
development_stage_ontology_term_id
tissue_type
cell_type
assay
disease
organism
sex
tissue
self_reported_ethnicity
development_stage
Gastric_Tumor116329 cells Normal_Adjacent30911 cells HCATisStabAug1771848592166 cells Kumar et al. 2022147240 cells Nowicki-Osuch et al. 202275417 cells Zhang et al. 201943014 cells Wang et. al. 202014237 cells Sathe et al. 202013915 cells Gastric Cancer147240 cells Foveolar_Intermediate22003 cells Foveolar_Differentiated17336 cells Enterocytes_Intermediate13486 cells Intestinal_Undifferentiated8648 cells Enteroendocrine_CHGA3838 cells Enteroendocrine_GAST1536 cells Enteroendocrine_GHRL1471 cells Foveolar_Intermediate18362 cells Foveolar_Differentiated13276 cells Enterocytes_Intermediate12127 cells Intestinal_Undifferentiated7547 cells Enteroendocrine_CHGA2793 cells Enteroendocrine_GAST1413 cells IgA1_IgA2_IGKappa1273 cells Enteroendocrine_GHRL1179 cells Arterial capillary728 cells Macrophages_Activated488 cells NK-cells_Gastric361 cells Mast_Cells_Activated268 cells NK-cells_Intestine245 cells IgA2High_IGKappa240 cells IgG_IGM_IGLambda143 cells UBERON:0001161211130 cells UBERON:001347328694 cells UBERON:000116218832 cells UBERON:000765012771 cells MONDO:0001056116329 cells NCBITaxon:9606293823 cells Mixed intestinal and diffuse15126 cells IM with chronic gastritis35395 cells Chronic gastritis only13416 cells No IM, Chronic gastritis & HGD7241 cells IM with chronic gastritis & LGD3840 cells Chronic gastritis with IM3459 cells Moderately extensive IM2247 cells Loss of MLH1/PMS221675 cells loss of MLH1/PMS21603 cells HsapDv:000015626379 cells HsapDv:000016225925 cells HsapDv:000016120053 cells HsapDv:000015013697 cells HsapDv:000020812241 cells HsapDv:000020912066 cells HsapDv:000014211926 cells HsapDv:000016711332 cells HsapDv:000016810840 cells foveolar cell of stomach31638 cells epithelial cell of esophagus28360 cells mucous neck cell8983 cells IgA plasma cell5304 cells activated CD8-positive, alpha-beta T cell4882 cells intestine goblet cell4123 cells natural T-regulatory cell3254 cells enteroendocrine cell2793 cells gamma-delta T cell2470 cells vein endothelial cell1968 cells type G enteroendocrine cell1413 cells endothelial cell of artery1255 cells CD4-positive helper T cell1181 cells P/D1 enteroendocrine cell1179 cells glandular cell of esophagus1108 cells capillary endothelial cell728 cells natural killer cell606 cells gastric cancer116329 cells gastric intestinal metaplasia27462 cells Barrett esophagus10952 cells body of stomach211130 cells lower esophagus28694 cells cardia of stomach18832 cells esophagogastric junction12771 cells submucosal esophageal gland4006 cells 62-year-old human stage26379 cells 68-year-old human stage25925 cells 67-year-old human stage20053 cells 56-year-old human stage13697 cells 82-year-old human stage12241 cells 83-year-old human stage12066 cells 48-year-old human stage11926 cells 73-year-old human stage11332 cells 74-year-old human stage10840 cells 55-year-old human stage8595 cells 60-year-old human stage7907 cells 65-year-old human stage7399 cells 36-year-old human stage7241 cells 71-year-old human stage7129 cells 77-year-old human stage6957 cells 69-year-old human stage6866 cells 66-year-old human stage6810 cells 86-year-old human stage6701 cells 70-year-old human stage6169 cells 80-year-old human stage5812 cells 58-year-old human stage5793 cells 53-year-old human stage5426 cells 45-year-old human stage5091 cells 51-year-old human stage4471 cells 41-year-old human stage4414 cells 63-year-old human stage4218 cells 57-year-old human stage3589 cells 64-year-old human stage3459 cells 43-year-old human stage3386 cells 42-year-old human stage3227 cells 29-year-old human stage3057 cells 27-year-old human stage2697 cells 84-year-old human stage2330 cells 34-year-old human stage2166 cells 88-year-old human stage1603 cells 54-year-old human stage1486 cells 50-year-old human stage890 cells 80 year-old and over human stage560 cells Analyze this study
Source data
https://cellxgene.cziscience.com/collections/a18474f4-ff1e-4864-af69-270b956cee5b
Alias names
EGAD00001010074, PMID36929873, PMC10236154
Cite this study
Nowicki-Osuch, K., Zhuang, L., Cheung, T.S., Black, E.L., Masqué-Soler, N., Devonshire, G., Redmond, A.M., Freeman, A., di Pietro, M., Pilonis, N. and Januszewicz, W., 2023. Single-cell RNA sequencing unifies developmental programs of esophageal and gastric intestinal metaplasia. Cancer discovery, 13(6), pp.1346-1363. https://doi.org/10.1158/2159-8290.CD-22-0824
