Abstract
SummaryDevelopment 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.
Highlights
The intestine is the largest barrier organ in the body, coordinating nutritional requirements and immunity in symbiosis with intestinal microbiota (Soderholm and Pedicord, 2019)
Between 8–12 post-conceptual weeks (PCW), the pseudo-stratified epithelium warps, generating villus and crypt structures composed of diverse differentiated epithelial cell types and establishing their self-renewing circuits maintained by epithelial stem cells (ISCs) (Gao et al, 2009; Que et al, 2007; Sherwood et al, 2009; Spence et al, 2011)
In early development (
Summary
Fawkner-Corbett et al chart human intestinal morphogenesis across time, location, and cellular compartments using a combination of single-cell RNA sequencing and spatial transcriptomics. The resulting online searchable atlas describes the principles of crypt-villus axis formation as well as neural, vascular, mesenchymal morphogenesis, and immune populations of the developing gut. Highlights d Multimodal atlas of human intestinal development maps 101 cell types onto tissue d Charts developmental origins of diverse cellular compartments and their progenitors d Functional diversity of fibroblasts in stem cell, vasculature, and GALT formation d Resource applied to interrogate pathology of in utero intestinal diseases. February 4, 2021 a 2021 The Authors.
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