Although 3D human ‘somitoids’ have recently been reported, the somite-like structures are not sequentially formed 19. However, somites or epithelial structures are not formed in those human stem cell-derived models.
Regarding human somitogenesis, several groups have induced PSM and somite cell fates from human pluripotent stem cells in 2D cultures and recapitulated the segmentation clock 6, 7, 8, 9, 16, 17, 18. Mouse ESC-derived trunk-like structures (TLSs) form both the neural tube and bilateral somites 15. Gastruloids are ESC-derived embryonic organoids that mimic early developmental events, including three-germ layer differentiation and axis patterning 11, 12, 13, and mouse gastruloids embedded in an extracellular matrix (ECM) surrogate, Matrigel, form a string of single somites 14.
PSM-like flat tissues made from mouse embryonic stem cells (ESCs) display the segmentation clock accompanied by tissue boundary formation 10. Several aspects of somitogenesis have recently been recapitulated in vitro with pluripotent stem cells. The timing of sequential somitogenesis is controlled by the segmentation clock, a molecular oscillator that peaks its activity every 5-6 hours in humans 2, 5, 6, 7, 8, 9. The somite formation, or somitogenesis, starts around day 20 after fertilization (Carnegie stage 9) in human embryos, and a total of ~40 pairs of somites are formed 4. The anterior PSM cells eventually form spherical epithelial somites surrounding a core of mesenchymal cells. Bilateral pairs of somites periodically bud off from the presomitic mesoderm (PSM) along the anterior-posterior axis: as the mesenchymal cells migrate from the posterior PSM region near the tailbud to the anterior PSM region, they undergo a mesenchymal-epithelial transition (MET), acquiring the apical-basal polarity and elongated shapes. Somites are transient blocks of cells that give rise to a variety of tissues, including the vertebrae, rib cage, skeletal muscle, and part of the skin, in vertebrate embryos 1, 2, 3. Somitoids provide a novel platform to study human somitogenesis. The amount of WNT signaling instructs the proportion of mesodermal lineages in somitoids.
The size of somites is rather constant, irrespective of the initial cell number. Matrigel is essential for epithelialization but dispensable for the differentiation into somite cells. The resulting somites show anterior-posterior and apical-basal polarities. Somitoids display clear oscillations of the segmentation clock that coincide with the segmentation of the presomitic mesoderm. Here, we report the generation of human somitoids, organoids that periodically form pairs of epithelial somite-like structures. However, an in vitro model for human somitogenesis coupled with the segmentation clock and epithelialization is still missing. The process of somitogenesis has recently been recapitulated with murine and human pluripotent stem cells. During embryonic development, epithelial cell blocks called somites are periodically formed according to the segmentation clock, becoming the foundation for the segmental pattern of the vertebral column.
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