Líffræðifélag Íslands - biologia.is
Líffræðiráðstefnan 2025
Erindi/veggspjald / Talk/poster E92
Höfundar / Authors: Stefán Pétursson (1, 2), Juan Ouyang (1, 2), Afrooz Razi (2), Kasper D. Hansen (2), Katrín Möller (1, 2), Hans Tómas Björnsson (1, 2, 4)
Starfsvettvangur / Affiliations: 1. Louma G. Laboratory of Epigenetic Resesarch, University of Iceland, Reykjavik, Iceland. 2. Faculty of Medicine, School of Health Sciences, University of Iceland, Reykjavik, Iceland. 3. Department of Biostatistics, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205. 4. Landspitali University Hospital, Reykjavik, Iceland
Kynnir / Presenter: Stefán Pétursson
Mendelian Disorders of the Epigenetic Machinery (MDEMs) are caused by mutations in chromatin regulators and share overlapping neurodevelopmental features. The mechanisms by which disruption of the epigenetic machinery (EM) leads to these outcomes remain poorly understood. During neurodevelopment, neuronal progenitor cells (NPCs) sequentially undergo expansion, neurogenic, and gliogenic phases, where the timing of each phase is essential. Increasing evidence suggests that the epigenetic machinery (EM) plays an important role in the timing of these phases, potentially causing structural abnormalities in the brain when disrupted. To test this, we examined murine NPC differentiation after loss of EM function. A preliminary screen of 27 EM gene knockouts in murine NPCs revealed 16 that altered neuronal or astrocytic marker expression. For six genes, lineage shifts were confirmed by immunofluorescence. We further validated our findings using NPCs, isolated from a Wiedemann-Steiner syndrome mouse model (Kmt2a-deficiency) and observed premature neuronal differentiation, consistent with the smaller dentate gyrus and neurological deficits previously described in the model. Our findings show that EM disruption leads to changes in the differentiation of murine NPCs, providing a potential shared mechanism for neurodevelopmental impairment across multiple MDEMs.