Single-Cell Sequencing of Developing Human Gut Reveals Transcriptional Links to Childhood Crohn’s Disease
Rasa Elmentaite, Alexander D.B. Ross, Kenny Roberts, Kylie R. James, Daniel Ortmann, Tomás Gomes, Komal Nayak, Liz Tuck, Sophie Pritchard, Omer Ali Bayraktar, Robert Heuschkel, Ludovic Vallier, Sarah A. Teichmann, Matthias Zilbauer
Abstract
Human gut development requires the orchestrated interaction of differentiating cell types. Here, we generate an in-depth single-cell map of the developing human intestine at 6–10 weeks post-conception. Our analysis reveals the transcriptional profile of cycling epithelial precursor cells; distinct from LGR5-expressing cells. We propose that these cells may contribute to differentiated cell subsets via the generation of LGR5-expressing stem cells and receive signals from surrounding mesenchymal cells. Furthermore, we draw parallels between the transcriptomes of ex vivo tissues and in vitro fetal organoids, revealing the maturation of organoid cultures in a dish. Lastly, we compare scRNA-seq profiles from pediatric Crohn’s disease epithelium alongside matched healthy controls to reveal disease-associated changes in the epithelial composition. Contrasting these with the fetal profiles reveals the re-activation of fetal transcription factors in Crohn’s disease. Our study provides a resource available at www.gutcellatlas.org, and underscores the importance of unraveling fetal development in understanding disease.
Datasets
1. Fetal Human Gut (6-11 PCW)
Metadata
Enrichment_fraction
PCW
Purification
Sample
cell_type_group
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organism_ontology_term_id
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4918STDY77189733367 cells 4918STDY73215153218 cells 4918STDY76937633191 cells 4918STDY73175853093 cells 4918STDY73175872655 cells 4918STDY74269062649 cells 4918STDY77189742589 cells 4918STDY77177892303 cells 4918STDY73215142294 cells 4918STDY77177882252 cells 4918STDY77189722149 cells 4918STDY73215132036 cells 4918STDY77177872023 cells 4918STDY74212982006 cells 4918STDY73175861969 cells 4918STDY74269051889 cells 4918STDY76937621734 cells 4918STDY77177851696 cells 4918STDY74269081689 cells 4918STDY76937591688 cells 4918STDY77177831616 cells 4918STDY74212971551 cells 4918STDY76937581525 cells 4918STDY76937601385 cells 4918STDY77189751287 cells 4918STDY76937571278 cells 4918STDY76937611199 cells 4918STDY74269091168 cells 4918STDY77189761064 cells 4918STDY74269071060 cells Small intestinal Epi8906 cells Uniform progenitors4064 cells Neural crest cells3141 cells Enteric neurons1804 cells Smooth muscle cells7154 cells Early enterocyte4157 cells G2M/S enterocytes3935 cells Neural crest cells3141 cells Uniform progenitors2659 cells FOXL1+ fibroblasts2622 cells WNT4+ fibroblasts2220 cells Enteric neurons1804 cells Venous endothelial cell1704 cells Serosa/mesothelial cells797 cells Interstitial cells of Cajal752 cells FRZB+ fibroblasts383 cells Arterial endothelial cell372 cells NTS+ epithelial cells182 cells Lymphatic endothelial cell104 cells BEST4+ enterocyte83 cells HsapDv:000003037249 cells NCBITaxon:960662849 cells UBERON:841000021592 cells UBERON:000115521147 cells UBERON:000211620110 cells mesodermal cell19753 cells enteric smooth muscle cell7154 cells neural crest cell3141 cells progenitor cell2659 cells colon epithelial cell2354 cells myofibroblast cell1919 cells vein endothelial cell1704 cells hematopoietic cell1033 cells mesothelial cell797 cells interstitial cell of Cajal752 cells intestine goblet cell504 cells enteroendocrine cell383 cells endothelial cell of artery372 cells endothelial cell of lymphatic vessel104 cells duodeno-jejunal junction21592 cells Carnegie stage 2337249 cells Carnegie stage 177548 cells Carnegie stage 185461 cells 10th week post-fertilization human stage4356 cells Carnegie stage 224318 cells Carnegie stage 193917 cells 2. Paediatric Human Gut (4-14y)
Metadata
Type
batch
annotation_V2
inferred state
assay_ontology_term_id
cell_type_ontology_term_id
development_stage_ontology_term_id
disease_ontology_term_id
self_reported_ethnicity_ontology_term_id
organism_ontology_term_id
sex_ontology_term_id
tissue_ontology_term_id
donor_id
suspension_type
tissue_type
cell_type
assay
disease
organism
sex
tissue
self_reported_ethnicity
development_stage
Paediatric biopsy22502 cells 4918STDY79010963430 cells 4918STDY73334562582 cells 4918STDY79624702360 cells 4918STDY74478251911 cells 4918STDY72739651602 cells 4918STDY73894311499 cells 4918STDY79827031319 cells 4918STDY79237441254 cells 4918STDY77026801143 cells 4918STDY72748391065 cells 4918STDY72739641008 cells IgG plasma cell1137 cells IgA plasma cell1100 cells early enterocyte837 cells Venous endothelial cell401 cells Arterial endothelial cell355 cells IL2RG+ enterocyte (M cell)249 cells Activated B cell218 cells Lymphatic endothelial cell174 cells BEST4 enterocyte119 cells Cycling plasma cell78 cells Cycling myeloid cells40 cells NCBITaxon:960622502 cells UBERON:000211622502 cells CD4-positive, alpha-beta T cell1258 cells intestinal crypt stem cell1190 cells IgG plasma cell1137 cells IgA plasma cell1100 cells intestine goblet cell1049 cells transit amplifying cell600 cells gamma-delta T cell490 cells vein endothelial cell401 cells conventional dendritic cell398 cells endothelial cell of artery355 cells CD8-positive, alpha-beta T cell340 cells activated CD4-positive, alpha-beta T cell, human301 cells T follicular helper cell232 cells endothelial cell of lymphatic vessel174 cells myofibroblast cell171 cells regulatory T cell137 cells enteroendocrine cell71 cells dendritic cell, human43 cells intestinal tuft cell33 cells plasmacytoid dendritic cell23 cells 4-year-old human stage4682 cells 12-year-old human stage3986 cells 9-year-old human stage3614 cells 11-year-old human stage3430 cells 10-year-old human stage2390 cells 6-year-old human stage1911 cells 13-year-old human stage1749 cells 14-year-old human stage740 cells Analyze this study
Source data
https://cellxgene.cziscience.com/collections/17481d16-ee44-49e5-bcf0-28c0780d8c4a
Alias names
E-MTAB-8901, PMID33290721, PMC7762816
Cite this study
Elmentaite, R., Ross, A.D., Roberts, K., James, K.R., Ortmann, D., Gomes, T., Nayak, K., Tuck, L., Pritchard, S., Bayraktar, O.A. and Heuschkel, R., 2020. Single-cell sequencing of developing human gut reveals transcriptional links to childhood Crohn’s disease. Developmental cell, 55(6), pp.771-783. https://doi.org/10.1016/j.devcel.2020.11.010
