Dynamic allele usage of X-linked genes ameliorates neurodevelopmental disease phenotypes in brain organoids.

ABSTRACT: While random X-chromosome inactivation in female cells of placental mammals silences one allele of the majority of X-chromosomal genes, a considerable fraction is only incompletely and variably inactivated. Human model systems to study the dynamics of incomplete X-inactivation are limited mostly to postmortem tissue, thereby disregarding developmental trajectories. Here, we used clonal human female induced pluripotent stem cells to track allele-specific expression of X-chromosomal genes along neural differentiation. We discovered dynamic reactivation and late-silencing of gene expression from the inactive X-chromosome leading to differentiation-induced locus- and lineage-specific usage of the two X-chromosomal alleles. In brain organoids modeling Opitz BBB/G syndrome, an X-linked neurodeve

SUBMITTER: Bertin M 

PROVIDER: S-EPMC12808108 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature