Summary 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. We show that pre-differentiation culture medium impacts the developmental potential of induced pluripotent stem cells (iPSCs), with StemFit medium and Matrigel embedding outperforming mTeSR Plus medium in generating robust somite-like structures. Strikingly, these differences arise despite only subtle changes in transcriptomic and time-resolved proteomic profiles. P300-based proximity labeling also reveals a largely overlapping set of chromatin-associated regulators across iPSC conditions. In somitoids, enhancer-associated profiling highlights factors linked to somitogenesis, including MESP2 and TBX6. Knockout of three identified regulators, BPTF, RBPJ, and CITED2, demonstrate their essential roles in somite formation. Together, these findings highlight how culture conditions and enhancer-associated networks influence early human development and demonstrate somitoids as a scalable system for functional genomics.
Maria Teresa Alejo-Vinogradova, Y. E. Strøm, L. Lamers et al.· Stem Cell Reports· 0 citations
Epigenetic regulation is essential for development and adaptation across eukaryotes. However, a comprehensive overview of the molecular framework of chromatin-mediated regulation, particularly in non-model organisms, is lacking. Here, we present a systematic proteomic characterization of the chromatin domains in P. falciparum, an ancient human pathogen with a unique genome composition and epigenetic blueprint. We adapted and employed three proximity-labeling approaches to provide a high-confidence and comprehensive proteome of heterochromatin, euchromatin, and (peri)centromeric chromatin comprising 214 proteins, including both expected and new chromatin components. Characterization of 20 proteins validated our approach and uncovered (1) a protein influencing parasite transmission, (2) complexes relevant for histone variant exchange and chromatin-RNA interactions, and (3) the so-far believed-to-be-absent spindle assembly checkpoint and the corresponding Bub1-like kinase. This study hence offers a reference proteome of the chromatin domains and a resource to uncover novel chromatin biology.
Gala Ramón-Zamorano, Sheila Mainye, Jessica Kimmel et al.· Cell Host and Microbe· 0 citations
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