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

Publikation: Beitrag in FachzeitschriftArtikelBegutachtung

56 Zitate (Scopus)

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.

OriginalspracheEnglisch
Seiten (von - bis)3281-3298.e22
FachzeitschriftCell
Jahrgang184
Ausgabenummer12
DOIs
PublikationsstatusVeröffentlicht - 10 Juni 2021
Extern publiziertJa

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