Paraxial mesoderm organoids model development of human somites
- Dana-Farber Cancer Institute, United States
- KU Leuven, Belgium
- Harvard Medical School, United States
Abstract
During the development of the vertebrate embryo, segmented structures called somites are periodically formed from the presomitic mesoderm (PSM), and give rise to the vertebral column. While somite formation has been studied in several animal models, it is less clear how well this process is conserved in humans. Recent progress has made it possible to study aspects of human paraxial mesoderm development such as the human segmentation clock in vitro using human pluripotent stem cells (hPSCs), however, somite formation has not been observed in these monolayer cultures. Here, we describe the generation of human paraxial mesoderm (PM) organoids from hPSCs (termed Somitoids), which recapitulate the molecular, morphological and functional features of paraxial mesoderm development, including formation of somite-like structures in vitro. Using a quantitative image-based screen, we identify critical parameters such as initial cell number and signaling modulations that reproducibly yielded formation of somite-like structures in our organoid system. In addition, using single-cell RNA sequencing and 3D imaging, we show that PM organoids both transcriptionally and morphologically resemble their in vivo counterparts and can be differentiated into somite derivatives. Our organoid system is reproducible and scalable, allowing for the systematic and quantitative analysis of human spinal cord development and disease in vitro.
Data availability
Sequencing data has been deposited in GEO under accession code GSE194214; All data used to generate the figures are included in the manuscript as Source Data files
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Paraxial mesoderm organoids model development of human somitesNCBI Gene Expression Omnibus, GSE194214.
Article and author information
Author details
Funding
National Institutes of Health (P01GM099117)
- Christoph Budjan
- Sahand Hormoz
National Heart, Lung, and Blood Institute (R01HL158269)
- Christoph Budjan
- Sahand Hormoz
Chan Zuckerberg Initiative (2018-183143)
- Christoph Budjan
- Sahand Hormoz
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2022, Budjan et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Paraxial mesoderm organoids model development of human somites
eLife 11:e68925.
https://doi.org/10.7554/eLife.68925
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