From stem cells to somites: revealing genetic and exogenous factors of human embryogenesis

Stem cell-based human embryo models offer an ethically tractable platform for studying early human development. This study employs somitoids, three-dimensional models of human somitogenesis, to investigate how transcriptional programs and culture conditions influence somite formation and segmentation. Pre-differentiation conditions strongly impact developmental potential, with StemFit medium outperforming mTeSR Plus in generating robust somite-like structures, despite minimal differences in transcriptomic and proteomic profiles. RNA-seq was performed on iPSCs cultured in mTeSR Plus or StemFit medium, as well as on day 5 somitoids derived from these conditions. Additional RNA-seq analyses included wildtype, BPTF, RBPJ, and CITED2 knockout lines, and CITED2 rescue lines. These targets were selected based on p300 proximity labeling to functionally validate identified p300 proximity interactors. To confirm that the p300–miniTurbo fusion remained functional, ChIP-seq was performed on undifferentiated iPSCs cultured in mTeSR Plus medium. Together, our findings highlight somitoids as a robust and scalable system for studying gene regulation during early human development, enabling functional interrogation of key chromatin-associated regulators driving somitogenesis.

• Type: Gene Regulation Study
• Archive: European Genome-phenome Archive (EGA)