Cells of the human intestinal tract mapped across space and time
Rasa Elmentaite, Natsuhiko Kumasaka, Kenny Roberts, Aaron Fleming, Emma Dann, Hamish W. King, Vitalii Kleshchevnikov, Monika Dabrowska, Sophie Pritchard, Liam Bolt, Sara F. Vieira, Lira Mamanova, Ni Huang, Francesca Perrone, Issac Goh Kai’En, Steven N. Lisgo, Matilda Katan, Steven Leonard, Thomas R. W. Oliver, C. Elizabeth Hook, Komal Nayak, Lia S. Campos, Cecilia Domínguez Conde, Emily Stephenson, Justin Engelbert, Rachel A. Botting, Krzysztof Polanski, Stijn van Dongen, Minal Patel, Michael D. Morgan, John C. Marioni, Omer Ali Bayraktar, Kerstin B. Meyer, Xiaoling He, Roger A. Barker, Holm H. Uhlig, Krishnaa T. Mahbubani, Kourosh Saeb-Parsy, Matthias Zilbauer, Menna R. Clatworthy, Muzlifah Haniffa, Kylie R. James, Sarah A. Teichmann
Abstract
The cellular landscape of the human intestinal tract is dynamic throughout life, developing in utero and changing in response to functional requirements and environmental exposures. Here, to comprehensively map cell lineages, we use single-cell RNA sequencing and antigen receptor analysis of almost half a million cells from up to 5 anatomical regions in the developing and up to 11 distinct anatomical regions in the healthy paediatric and adult human gut. This reveals the existence of transcriptionally distinct BEST4 epithelial cells throughout the human intestinal tract. Furthermore, we implicate IgG sensing as a function of intestinal tuft cells. We describe neural cell populations in the developing enteric nervous system, and predict cell-type-specific expression of genes associated with Hirschsprung’s disease. Finally, using a systems approach, we identify key cell players that drive the formation of secondary lymphoid tissue in early human development. We show that these programs are adopted in inflammatory bowel disease to recruit and retain immune cells at the site of inflammation. This catalogue of intestinal cells will provide new insights into cellular programs in development, homeostasis and disease.
Datasets
1. Total - Cells of the human intestinal tract mapped across space and time
Metadata
donor_id
Diagnosis
Fraction
category
Age_group
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
suspension_type
hca_data_portal_donor_uuid
tissue_type
tissue_ontology_term_id
cell_type
assay
disease
organism
sex
tissue
self_reported_ethnicity
development_stage
Healthy adult124367 cells Pediatric healthy29594 cells Pediatric Crohn Disease27164 cells Red blood cells1391 cells Second trim_MLN8174 cells HsapDv:000009064079 cells HsapDv:000005247836 cells HsapDv:000004638323 cells HsapDv:000024035738 cells HsapDv:000004834177 cells HsapDv:000005327859 cells HsapDv:000004725420 cells HsapDv:000009816523 cells HsapDv:000023814430 cells HsapDv:000005414046 cells HsapDv:000002413416 cells HsapDv:000003011785 cells HsapDv:000002811026 cells HsapDv:000024110120 cells NCBITaxon:9606428469 cells ef21cf43-074e-4447-973a-bb283e29381d31569 cells 4dd5e941-f47d-453d-8726-6237b3dab4d127859 cells c6693ae1-f3ae-43d5-9431-1bc14b720a7927502 cells 4e654cf2-a45f-41ed-885b-91a03cc02a1723607 cells 7a7cbfae-b6c1-4561-bfb2-4068b082919621940 cells 31105af6-52fc-4ad5-9fd1-1a883cfe38b117193 cells e6d52130-0863-4936-8711-f96d92fb52eb16267 cells d2fea39e-97a7-4107-8582-431355042e0414716 cells d724f8a5-e655-4c05-b4ef-a1f3b19e2cbc14430 cells 7b9c04f3-86a2-4087-9ff9-740ec259096514046 cells 08b077ca-5f57-432c-a930-aa250fe38cea11785 cells 54c59671-394f-4163-b098-336d6b2c2e2610120 cells 508387b9-b1e7-460d-ac1a-dfed7016f52f8379 cells 48fb66e0-a26a-44ae-8253-91b76bc168408236 cells b9beeadb-d66e-49b3-a0d4-21b2b68b9a1c8227 cells 4d10fba8-c151-4da7-84ea-5e9986a960b77752 cells 91f2e38f-1490-4a05-ade6-5be2780b26867570 cells c16c0cc7-7bc8-41d4-b4df-3100ebd7e8b47507 cells b26d60fa-e6fe-4fcf-a495-7061c74a96396680 cells dbbccb5d-2fa2-4190-b368-d9785c87d49b5664 cells 9b2a3014-c6db-4426-8676-81b5ce2d93b25504 cells 0174ed20-c725-4755-bae7-ca99d17ab7b44799 cells e439f5cc-fd59-46a0-bdd8-6c61a5c1e0b24602 cells 50a3c4ae-f40e-4d5a-a9f5-3388391952a14084 cells cb6e49b3-74f8-4a60-85c8-0114fad51e6a4084 cells ad5eac20-9666-4b91-bfac-8bb7ac234c933558 cells 9c52bbf7-3970-428d-b79e-223d4777cb452560 cells 25f7101f-5cd1-42a3-8968-59a57a5fb1352369 cells debb79ce-8577-4106-9689-102bfeb138dc2354 cells eb437b76-1915-4f82-928b-7d3cef8285482312 cells 3c015e23-347a-4c1c-8289-3aa0d6d7bfa92081 cells 04a56e16-6555-4358-af61-88e160d3cb1a1761 cells 7b0c6639-a0d2-48ee-b3ed-7576c15133071353 cells b4843937-92aa-4ef9-b833-54799319c1d91072 cells UBERON:0002116171706 cells UBERON:000005945338 cells UBERON:000210844964 cells UBERON:000211444465 cells UBERON:000115532238 cells UBERON:000250918539 cells UBERON:000105218430 cells UBERON:000115911949 cells UBERON:000115711802 cells mesodermal cell64188 cells transit amplifying cell50024 cells enterocyte of colon37460 cells enteric smooth muscle cell18955 cells IgA plasma cell16882 cells colon epithelial cell14133 cells progenitor cell12732 cells intestine goblet cell8355 cells CD4-positive, alpha-beta T cell7643 cells myofibroblast cell6091 cells activated CD8-positive, alpha-beta T cell5738 cells capillary endothelial cell4959 cells epithelial cell4555 cells gamma-delta T cell4268 cells activated CD4-positive, alpha-beta T cell3948 cells regulatory T cell3923 cells vein endothelial cell3758 cells type EC enteroendocrine cell3259 cells oligodendrocyte precursor cell3257 cells migratory enteric neural crest cell2969 cells germinal center B cell2785 cells endothelial cell of lymphatic vessel2656 cells T follicular helper cell2501 cells CD8-positive, alpha-beta T cell2486 cells conventional dendritic cell2460 cells neuroblast (sensu Vertebrata)2355 cells mesothelial cell2204 cells natural killer cell1869 cells CD8-positive, alpha-beta memory T cell1841 cells inhibitory motor neuron1742 cells IgG plasma cell1596 cells endothelial cell of artery1568 cells interstitial cell of Cajal1404 cells primary sensory neuron (sensu Teleostei)1030 cells NKp44-negative group 3 innate lymphoid cell, human739 cells intestinal tuft cell737 cells T-helper 17 cell681 cells stromal cell of lamina propria of small intestine640 cells NKp44-positive group 3 innate lymphoid cell, human611 cells enteroendocrine cell485 cells precursor B cell426 cells plasmacytoid dendritic cell422 cells group 3 innate lymphoid cell413 cells mature NK T cell411 cells mesenchymal lymphangioblast410 cells CD34-positive, CD56-positive, CD117-positive common innate lymphoid precursor, human395 cells progenitor cell of endocrine pancreas336 cells inflammatory macrophage333 cells type I enteroendocrine cell227 cells follicular dendritic cell203 cells common lymphoid progenitor186 cells type D enteroendocrine cell143 cells type L enteroendocrine cell118 cells mucosal invariant T cell104 cells group 2 innate lymphoid cell48 cells type N enteroendocrine cell44 cells type B pancreatic cell31 cells large intestine45338 cells small intestine44964 cells mesenteric lymph node18539 cells transverse colon11802 cells ascending colon7007 cells vermiform appendix6378 cells descending colon3807 cells 25-44 year-old human stage64079 cells 15th week post-fertilization human stage47836 cells 9th week post-fertilization human stage38323 cells sixth decade human stage35738 cells 11th week post-fertilization human stage34177 cells 16th week post-fertilization human stage27859 cells 10th week post-fertilization human stage25420 cells 4-year-old human stage16523 cells fourth decade human stage14430 cells 17th week post-fertilization human stage14046 cells Carnegie stage 1713416 cells Carnegie stage 2311785 cells Carnegie stage 2111026 cells seventh decade human stage10120 cells 12-year-old human stage9996 cells 12th week post-fertilization human stage8379 cells Carnegie stage 197570 cells Carnegie stage 227507 cells 9-year-old human stage7359 cells 11-year-old human stage6680 cells 13-year-old human stage5674 cells 6-year-old human stage4084 cells 10-year-old human stage4073 cells 14-year-old human stage2369 cells Analyze this study
Source data
https://cellxgene.cziscience.com/collections/e33ffcd3-7cbf-4b8c-b0f4-85587ad5019a
Alias names
E-MTAB-9543, PMID34497389, PMC8426186
Cite this study
Elmentaite, R., Kumasaka, N., Roberts, K., Fleming, A., Dann, E., King, H.W., Kleshchevnikov, V., Dabrowska, M., Pritchard, S., Bolt, L. and Vieira, S.F., 2021. Cells of the human intestinal tract mapped across space and time. Nature, 597(7875), pp.250-255. https://doi.org/10.1038/s41586-021-03852-1
