Charting human development using a multi-endodermal organ atlas and organoid models

Qianhui Yu, Umut Kilik, Emily M. Holloway, Yu-Hwai Tsai, Christoph Harmel, Angeline Wu, Joshua H. Wu, Michael Czerwinski, Charlie J. Childs, Zhisong He, Meghan M. Capeling, Sha Huang, Ian A. Glass, Peter D.R. Higgins, Barbara Treutlein, Jason R. Spence, J. Gray Camp

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.

Datasets

1. Developing Human Atlas
Metadata
mapped_reference_assembly
alignment_software
donor_id
self_reported_ethnicity_ontology_term_id
donor_living_at_sample_collection
organism_ontology_term_id
sample_uuid
sample_preservation_method
tissue_ontology_term_id
development_stage_ontology_term_id
sample_derivation_process
sample_source
suspension_derivation_process
suspension_dissociation_reagent
suspension_uuid
suspension_type
library_uuid
assay_ontology_term_id
library_starting_quantity
sequencing_platform
cell_type_ontology_term_id
author_cell_type
cell_state
disease_ontology_term_id
sex_ontology_term_id
Sample
Major_cell_type
annotated_organ
annotated_tissue
orig_study
tissue_type
cell_type
assay
disease
organism
sex
tissue
self_reported_ethnicity
development_stage
hg19155232 cells
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Charting human development using a multi-endodermal organ atlas and organoid models

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Dataset 1
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Source data

https://cellxgene.cziscience.com/collections/dfc09a93-bce0-4c77-893d-e153d1b7f9fa

Alias names

E-MTAB-10187, E-MTAB-10268, PMID34019796, PMC8208823

Cite this study

Yu, Q., Kilik, U., Holloway, E.M., Tsai, Y.H., Harmel, C., Wu, A., Wu, J.H., Czerwinski, M., Childs, C.J., He, Z. and Capeling, M.M., 2021. Charting human development using a multi-endodermal organ atlas and organoid models. Cell, 184(12), pp.3281-3298. https://doi.org/10.1016/j.cell.2021.04.028