Cell atlas of antigen-presenting and stromal cells from the human intestine
Thomas M. Fenton, Line Wulff, ProfileGareth-Rhys Jones, Julien Vandamme, ProfilePeter B. Jørgensen, ProfileCalum C. Bain, Julie Lee, Jose MG. Izarzugaza, Kirstine G. Belling, ProfileGwo-Tzer Ho, Ole H. Nielsen, ProfileLene B. Riis, ProfileTune H. Pers, Henrik L. Jakobsen, ProfileAllan M. Mowat, ProfileSøren Brunak, ProfileWilliam W. Agace
Abstract
Mononuclear phagocytes (MNP), including macrophages and classical dendritic cells (cDC), are highly heterogeneous cells with distinct functions. Understanding MNP complexity in the intestinal lamina propria (LP), particularly in humans, has proved difficult due to the expression of overlapping phenotypic markers and the inability to isolate these cells without contamination from gut-associated lymphoid tissues (GALT). Here, we exploited our novel method for isolation of human GALT-free LP to carry out single-cell (sc)RNA-seq, CITE-seq and flow cytometry analysis of human ileal and colonic LP MNPs. As well as classical monocytes, non-classical monocytes, mature macrophage subsets, cDC1s, and cDC2s, we identified a CD1c+ cDC subset with features of both cDC2 and monocytes, which were transcriptionally similar to the recently described cDC3. While similar MNP subsets were present in both ileal and colonic LP, the proportions and transcriptional profiles of these populations differed between these sites and in diseased states, indicating local specialization and environmental imprinting. Using computational trajectory tools, we identified putative early committed pre-cDC subsets and developmental intermediates of mature cDC1, cDC2 and cDC3, as well as monocyte–to-macrophage trajectories. Collectively, our results provide novel insights into the heterogeneity and development of intestinal LP MNP and an important framework for studying the role of these populations in intestinal homeostasis and disease.
Datasets
1. Lamina propria Epcam-CD235ab-CD45-
Metadata
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NCBITaxon:960632926 cells HsapDv:000015319456 cells HsapDv:000020613470 cells P9-SI-LP-CD45neg12616 cells P8-CO-LP-CD45neg10799 cells P8-SI-LP-CD45neg8657 cells P9-CO-LP-CD45neg854 cells P8_Epcam-CD235ab-CD45-19456 cells P9_Epcam-CD235ab-CD45-13470 cells UBERON:000123821273 cells UBERON:001118911653 cells lamina propria of small intestine21273 cells lamina propria of large intestine11653 cells 59-year-old human stage19456 cells 80-year-old human stage13470 cells 2. Lamina propria CD45+CD3-CD19-HLADR+
Metadata
organism_ontology_term_id
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NCBITaxon:960628758 cells HsapDv:000015713030 cells UBERON:001118919321 cells P3-CO-LP-HLADR+4969 cells P3-SI-LP-HLADR+4373 cells P5-CO-LP-HLADR+3688 cells P6-CO-LP-HLADR+3614 cells P2-CO-LP-HLADR+3393 cells P2-SI-LP-HLADR+2684 cells P4-CO-LP-HLADR+2461 cells P1-SI-LP-HLADR+1558 cells P1-CO-LP-HLADR+1196 cells mononuclear phagocyte28758 cells lamina propria of large intestine19321 cells lamina propria of small intestine9437 cells 63-year-old human stage13030 cells 74-year-old human stage6077 cells 83-year-old human stage3614 cells 76-year-old human stage3283 cells 66-year-old human stage2754 cells 3. Lamina propria Epcam-CD235ab-CD45-CD31-
Metadata
organism_ontology_term_id
self_reported_ethnicity_ontology_term_id
development_stage_ontology_term_id
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NCBITaxon:960617706 cells HsapDv:000016617706 cells P7-CO-LP-CD45neg9289 cells P7-SI-LP-CD45neg8417 cells P7_Epcam-CD235ab-CD45-CD31-17706 cells lamina propria of large intestine9289 cells lamina propria of small intestine8417 cells 72-year-old human stage17706 cells 4. Submucosa Epcam-CD235ab-CD45-CD31-
Metadata
organism_ontology_term_id
self_reported_ethnicity_ontology_term_id
development_stage_ontology_term_id
sex_ontology_term_id
cell_type_ontology_term_id
disease_ontology_term_id
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assay_ontology_term_id
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disease
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sex
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NCBITaxon:960616338 cells HsapDv:000016616338 cells P7-SI-SM-CD45neg9200 cells P7-CO-SM-CD45neg7138 cells P7_Epcam-CD235ab-CD45-CD31-16338 cells submucosa of ileum9200 cells submucosa of ascending colon7138 cells 72-year-old human stage16338 cells Analyze this study
Source data
https://cellxgene.cziscience.com/collections/0c3f148e-02ff-4c81-8946-29beaaf5fa59
Alias names
Cell atlas of antigen-presenting and stromal cells from the human intestine
Cite this study
Fenton, T.M., Wulff, L., Jones, G.R., Vandamme, J., Jørgensen, P.B., Bain, C.C., Lee, J., Izarzugaza, J.M., Belling, K.G., Ho, G.T. and Nielsen, O.H., 2021. High-dimensional profiling demonstrates complexity, tissue imprinting, and lineage-specific precursors within the mononuclear phagocyte compartment of the human intestine. bioRxiv, pp.2021-03. https://doi.org/10.1101/2021.03.28.437379
