Journal
CELL
Volume 184, Issue 3, Pages 810-+Publisher
CELL PRESS
DOI: 10.1016/j.cell.2020.12.016
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Categories
Funding
- Medical Research Council (Developmental Human Cell Atlas consortium) [MR/SO36377/1]
- Oxford NIHR Biomedical Research Centre
- Wellcome Investigator Award [219523/Z/19/Z]
- UK Medical Research Council
- Wellcome Trust [216419/Z/19/Z]
- BMS
- Lee Placito Medical Fund
- NIHR Clinical Research Network (CRN) Thames Valley
- NIHR-Senior Investigator Award
- Wellcome Trust [219523/Z/19/Z] Funding Source: Wellcome Trust
- MRC [MC_UU_00008/7, MR/S036377/1, MR/M00919X/1, MC_PC_MR/S025952/1, MC_UU_12010/7] Funding Source: UKRI
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This study uses single-cell RNA sequencing and spatial transcriptomics to investigate human intestinal development, identifying various cell states, developmental programs, and differentiation hierarchies. It provides insights into the formation of different cell types in the gut and offers valuable resources for further research in this field.
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.
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