Genomics

Dataset Information

0

The cholesterol transporter NPC1 is essential for epigenetic regulation and maturation of oligodendrocyte lineage cells ChIP-seq


ABSTRACT: Cholesterol is required for oligodendrocyte maturation and CNS myelination. Here, we demonstrate an essential role for the intracellular cholesterol transporter NPC1 in these processes. NPC1 functions in late endosomes and lysosomes to efflux unesterified cholesterol, and its deficiency causes Niemann-Pick disease Type C, an autosomal recessive lysosomal disorder characterized by progressive neurodegeneration and early death. To identify cell types and pathways affected early in pathogenesis, we performed single nuclear RNA-seq on the forebrain of Npc1-/- mice at P16. This analysis uncovered striking transcriptional changes in the oligodendrocyte lineage during the period of developmental myelination, accompanied by diminished maturation of myelinating oligodendrocytes. Unexpectedly, we identified a significant upregulation of genes associated with neurogenesis and synapse formation in Npc1-/- oligodendrocyte lineage cells, reflecting diminished gene silencing by H3K27me3 and H3K9me3. Npc1-/- oligodendrocyte progenitor cells reproduced impaired maturation in vitro and this phenotype was rescued by treatment with GSK-J4, a small molecule inhibitor of H3K27 demethylases. This study sought to determine the genes being directly impacted by the epigenetic dysfunction at H3K27.

ORGANISM(S): Mus musculus

PROVIDER: GSE219007 | GEO | 2023/05/31

REPOSITORIES: GEO

Dataset's files

Source:
Action DRS
Other
Items per page:
1 - 1 of 1

Similar Datasets

2023-05-31 | GSE221336 | GEO
2023-05-31 | GSE221609 | GEO
2015-04-20 | PXD001938 | Pride
2007-07-01 | GSE5944 | GEO
2016-07-27 | E-GEOD-75775 | biostudies-arrayexpress
2008-06-14 | E-GEOD-5944 | biostudies-arrayexpress
2012-04-16 | E-GEOD-36119 | biostudies-arrayexpress
2016-07-27 | GSE75775 | GEO
2024-05-26 | GSE223572 | GEO
2010-08-30 | E-GEOD-20450 | biostudies-arrayexpress