HCA Data Explorer

An organoid and multi-organ developmental cell atlas reveals multilineage fate specification in the human intestine

Updated November 10, 2021

Human intestinal organoids (HIOs) generated from pluripotent stem cells provide extraordinary opportunities to explore development and disease. Here, we generate a single-cell transcriptome reference atlas from HIOs and from multiple developing human organs to quantify the specificity of HIO cell fate acquisition, and to explore alternative fates. We identify epithelium-mesenchyme interactions, transcriptional regulators involved in cell fate specification, and stem cell maturation features in the primary tissue that are recapitulated in HIOs. We use an HIO time course to reconstruct the molecular dynamics of intestinal stem cell emergence, as well as the specification of multiple mesenchyme subtypes. We find that the intestinal master regulator CDX2 correlates with distinct phases of epithelial and mesenchymal development, and CDX2 deletion perturbs the differentiation of both intestinal epithelium and mesenchyme. Collectively our data provides a comprehensive and quantitative assessment of HIO development, and illuminates the molecular machinery underlying endodermal and mesodermal cell fate specification.

Barbara TreutleinETH Zurichbarbara.treutlein@bsse.ethz.ch
Jason SpenceUniversity of Michiganspencejr@med.umich.edu
Gray CampInstitute of Molecular and Clinical Opthalmology Baselgrayson.camp@iob.ch

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

Qianhui Yu1
Umut Kilik1
Emily M. Holloway2
Yu-Hwai Tsai2
Christoph Harmel1
Angeline Wu2
Joshua H. Wu2
Michael Czerwinski2
Charlie Childs2
Zhisong He3
Meghan M. Capeling2
Sha Huang2
Ian A. Glass4
Peter D.R. Higgins2
Barbara Treutlein (Principal Investigator)3
Jason Spence2
Gray Camp1
1Institute of Molecular and Clinical Opthalmology Basel
2University of Michigan
3ETH Zurich
4University of Washington
None

To reference this project, please use the following link:

https://explore.data.humancellatlas.org/projects/8ab8726d-81b9-4bd2-acc2-4d50bee786b4

Supplementary links are provided by contributors and represent items such as additional data which can’t be hosted here; code that was used to analyze this data; or tools and visualizations associated with this specific dataset.

1.http://www.jasonspencelab.com/protocols
None

For information regarding data sharing and data use, please see our Data Access Policy.

Analysis Portals

CZ CELLxGENECZ CELLxGENE

Project Label

Anorganoidandmulti-organdevelopmentalcellatlasreve

Species

Homo sapiens

Sample Type

3 sample types

Anatomical Entity

5 anatomical entities

Organ Part

9 organ parts

Selected Cell Types

Unspecified

Model Organ

intestine

Disease Status (Specimen)

Unspecified

Disease Status (Donor)

Unspecified

Development Stage

7 development stages

Library Construction Method

2 library construction methods

Nucleic Acid Source

single cell

Paired End

false

File Format

fastq

Cell Count Estimate

Unspecified

Donor Count

9
fastq395 file(s)