Transcriptomic Profiling of Developing Human Paraxial Mesoderm from 4.5-5 Weeks of Gestation Human Embryos
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE90876 | GEO | 2017/02/01
SECONDARY ACCESSION(S): PRJNA356265
REPOSITORIES: GEO
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Project description:Somites are transient embryonic structures consisting of hundreds of cells that bud off from the anterior tip of the presomitic mesoderm on each side of the neural tube. They give rise to the vertebrae and associated skeletal muscles, nerves, and blood vessels. To characterise the transcriptional changes that orchestrate mouse somitogenesis, we have generated coupled RNA-seq and ATAC-seq profiles of individual somites, across embryonic development. We collected the three most posterior pairs of somites, which correspond to those most recently segmented, from embryos containing 8, 18, 21, 25, 27 and 35 pairs of somites. The three somites are labelled I, II and III from the most posterior to the most anterior. From each pair, one somite was used for RNA-seq and the other one for ATAC-seq.
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Project description: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 somite formation 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.
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