A novel iPSC model of Bryant-Li-Bhoj neurodevelopmental syndrome demonstrates the role of histone H3.3 in neuronal differentiation and maturation.
Journal
bioRxiv : the preprint server for biology
ISSN: 2692-8205
Titre abrégé: bioRxiv
Pays: United States
ID NLM: 101680187
Informations de publication
Date de publication:
26 Aug 2024
26 Aug 2024
Historique:
medline:
10
9
2024
pubmed:
10
9
2024
entrez:
10
9
2024
Statut:
epublish
Résumé
Bryant-Li-Bhoj neurodevelopmental syndrome (BLBS) is neurogenetic disorder caused by variants in Here, we investigate how one BLBS-causative variant, In the 2D systems, we found dysregulation of both gene expression and chromatin accessibility of genes important for neuronal fate, maturation, and function in H3.3 L48R compared to control. Our work in 3D organoids corroborates these findings, demonstrating altered proportions of radial glia and mature neuronal cells. These data provide the first mechanistic insights into the pathogenesis of BLBS from a human-derived model of neurodevelopment, which suggest that the L48R increases
Sections du résumé
Background
UNASSIGNED
Bryant-Li-Bhoj neurodevelopmental syndrome (BLBS) is neurogenetic disorder caused by variants in
Methods
UNASSIGNED
Here, we investigate how one BLBS-causative variant,
Results
UNASSIGNED
In the 2D systems, we found dysregulation of both gene expression and chromatin accessibility of genes important for neuronal fate, maturation, and function in H3.3 L48R compared to control. Our work in 3D organoids corroborates these findings, demonstrating altered proportions of radial glia and mature neuronal cells.
Conclusions
UNASSIGNED
These data provide the first mechanistic insights into the pathogenesis of BLBS from a human-derived model of neurodevelopment, which suggest that the L48R increases
Identifiants
pubmed: 39253491
doi: 10.1101/2024.08.26.609745
pmc: PMC11382994
pii:
doi:
Types de publication
Journal Article
Preprint
Langues
eng