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
PHARC (polyneuropathy, hearing loss, ataxia, retinitis pigmentosa and cataracts) syndrome is a rare neurodegenerative inherited disorder characterized by a spectrum of these clinical phenotypes. Due to the considerable heterogeneity in the age of onset of the different clinical features and the similarities with other conditions, it is often misdiagnosed. Variants in the ABHD12 gene have been identified as a genetic cause of PHARC syndrome and are predicted to result in loss-of-function or severely reduced protein synthesis. ABHD12 (α/β-hydrolase domain-containing protein 12) is responsible for the breakdown of very-long-chain lysophosphatidylserines (VLC-lyso-PS). When ABHD12 is dysfunctional, VLC-lyso-PS accumulates in the brain, producing inflammation. In this study, the clinical phenotypes of five patients with molecularly confirmed ABHD12 pathogenic variants from Moorfields Eye Hospital together with those of 64 patients reported in the literature were analyzed to investigate genotype–phenotype correlations. We report a novel variant c.985del p.(His329Thrfs*57) associated with PHARC syndrome. Moreover, patients with two null variants in ABHD12 manifest more of the clinical features of PHARC syndrome than those with at least one missense variant. Our study shows the importance of a complete clinical and genetic diagnosis to enable accurate diagnosis and genetic counselling for affected individuals.
Sara Romero-Vázquez, Cécile Méjécase, A. Rodriguez-Martinez et al.· International Journal of Mol...· 0 citations
We use cookies to run the site and, with your consent, for analytics and to show ads.
See our Cookie Policy.
