Charting human development using a multi-endodermal organ atlas and organoid models
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Date
2021-06-10
Publication Type
Journal Article
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yes
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Abstract
Organs are composed of diverse cell types that traverse transient states during organogenesis. To interrogate this diversity during human development, we generate a single-cell transcriptome atlas from multiple developing endodermal organs of the respiratory and gastrointestinal tract. We illuminate cell states, transcription factors, and organ-specific epithelial stem cell and mesenchyme interactions across lineages. We implement the atlas as a high-dimensional search space to benchmark human pluripotent stem cell (hPSC)-derived intestinal organoids (HIOs) under multiple culture conditions. We show that HIOs recapitulate reference cell states and use HIOs to reconstruct the molecular dynamics of intestinal epithelium and mesenchyme emergence. We show that the mesenchyme-derived niche cue NRG1 enhances intestinal stem cell maturation in vitro and that the homeobox transcription factor CDX2 is required for regionalization of intestinal epithelium and mesenchyme in humans. This work combines cell atlases and organoid technologies to understand how human organ development is orchestrated.
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published
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Journal / series
Volume
184 (12)
Pages / Article No.
3281 - 3.298e+25
Publisher
Cell Press
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Date collected
Date created
Subject
Multi-organ cell atlas; Single-cell transcriptomics; Human endoderm development; Mesenchyme heterogeneity; Intestinal organoids; NRG1; CDX2
Organisational unit
09485 - Treutlein, Barbara / Treutlein, Barbara
Notes
Funding
758877 - Reconstructing human cortex development and malformation with single-cell transcriptomics (EC)
874606 - Molecular atlas of the brain across the human lifespan (EC)
192604 - Resolving and controlling brain patterning in human cerebral organoids (SNF)
874606 - Molecular atlas of the brain across the human lifespan (EC)
192604 - Resolving and controlling brain patterning in human cerebral organoids (SNF)