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

Organs are composed of diverse cell types, which 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 pluripotent stem cell-derived human intestinal organoids (HIOs) in multiple culture conditions. We show that HIOs recapitulate reference cell states, and use HIOs to reconstruct the molecular dynamics of the 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. Collectively, this work combines cell atlases and organoid technologies to understand how human organ development is orchestrated.

Contact

Camp Lab

Institute of Molecular and Clinical Ophthalmology Basel

University of Basel

Mittlere Strasse 91, CH-4031 Basel, Switzerland


Quantitative Developmental Biology Lab

Department of Biosystems Science and Engineering

ETH Z├╝rich

Mattenstrasse 26, 4058 Basel, Switzerland


Spence Lab

Department of Cell and Developmental Biology

University of Michigan Medical School

109 Zina Pitcher Place, Ann Arbor, Michigan 48109, USA



Developed by: Christoph Harmel

christoph.harmel@iob.ch