Spatiotemporal analysis of human intestinal development at single-cell resolution

David Fawkner-Corbett, Agne Antanaviciute, Kaushal Parikh, Marta Jagielowicz, Ana Sousa Gerós, Tarun Gupta, Neil Ashley, Doran Khamis, Darren Fowler, Edward Morrissey, Chris Cunningham, Paul R.V. Johnson, Hashem Koohy, Alison Simmons

Abstract

Development of the human intestine is not well understood. Here, we link single-cell RNA sequencing and spatial transcriptomics to characterize intestinal morphogenesis through time. We identify 101 cell states including epithelial and mesenchymal progenitor populations and programs linked to key morphogenetic milestones. We describe principles of crypt-villus axis formation; neural, vascular, mesenchymal morphogenesis, and immune population of the developing gut. We identify the differentiation hierarchies of developing fibroblast and myofibroblast subtypes and describe diverse functions for these including as vascular niche cells. We pinpoint the origins of Peyer’s patches and gut-associated lymphoid tissue (GALT) and describe location-specific immune programs. We use our resource to present an unbiased analysis of morphogen gradients that direct sequential waves of cellular differentiation and define cells and locations linked to rare developmental intestinal disorders. We compile a publicly available online resource, spatio-temporal analysis resource of fetal intestinal development (STAR-FINDer), to facilitate further work.

Datasets

1. Spatiotemporal analysis of human intestinal development at single-cell resolution: All cells
Metadata
Location
Genotype
Pool
Collection.ID
Cluster
disease_ontology_term_id
assay_ontology_term_id
self_reported_ethnicity_ontology_term_id
cell_type_ontology_term_id
organism_ontology_term_id
donor_id
development_stage_ontology_term_id
sex_ontology_term_id
tissue_ontology_term_id
suspension_type
tissue_type
cell_type
assay
disease
organism
sex
tissue
self_reported_ethnicity
development_stage
Distal colon27227 cells
TI24787 cells
Proximal colon21868 cells
Hindgut2710 cells
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Spatiotemporal analysis of human intestinal development at single-cell resolution

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Dataset 1
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Source data

https://cellxgene.cziscience.com/collections/60358420-6055-411d-ba4f-e8ac80682a2e

Alias names

GSE158702, PMID33406409, PMC7864098

Cite this study

Fawkner-Corbett, D., Antanaviciute, A., Parikh, K., Jagielowicz, M., Gerós, A.S., Gupta, T., Ashley, N., Khamis, D., Fowler, D., Morrissey, E. and Cunningham, C., 2021. Spatiotemporal analysis of human intestinal development at single-cell resolution. Cell, 184(3), pp.810-826. https://doi.org/10.1016/j.cell.2020.12.016