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Charting human development using a multi-endodermal organ atlas and organoid models.
- Source :
-
Cell [Cell] 2021 Jun 10; Vol. 184 (12), pp. 3281-3298.e22. Date of Electronic Publication: 2021 May 20. - Publication Year :
- 2021
-
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.<br />Competing Interests: Declaration of interests The authors declare no competing interests.<br /> (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)
- Subjects :
- CDX2 Transcription Factor metabolism
Cell Line
Epidermal Growth Factor pharmacology
Epithelial Cells cytology
Female
Gastrulation
Gene Deletion
Gene Expression Regulation, Developmental drug effects
Humans
Intestines embryology
Male
Mesoderm embryology
Middle Aged
Neuregulin-1 metabolism
Organ Specificity
Pluripotent Stem Cells cytology
Anatomy, Artistic
Atlases as Topic
Embryonic Development
Endoderm embryology
Models, Biological
Organoids embryology
Subjects
Details
- Language :
- English
- ISSN :
- 1097-4172
- Volume :
- 184
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- Cell
- Publication Type :
- Academic Journal
- Accession number :
- 34019796
- Full Text :
- https://doi.org/10.1016/j.cell.2021.04.028