Developmental alterations in Huntington's disease neural cells and pharmacological rescue in cells and mice.

ABSTRACT: Neural cultures derived from Huntington's disease (HD) patient-derived induced pluripotent stem cells were used for 'omics' analyses to identify mechanisms underlying neurodegeneration. RNA-seq analysis identified genes in glutamate and GABA signaling, axonal guidance and calcium influx whose expression was decreased in HD cultures. One-third of gene changes were in pathways regulating neuronal development and maturation. When mapped to stages of mouse striatal development, the profiles aligned with earlier embryonic stages of neuronal differentiation. We observed a strong correlation between HD-related histone marks, gene expression and unique peak profiles associated with dysregulated genes, suggesting a coordinated epigenetic program. Treatment with isoxazole-9, which targets key dysreg

SUBMITTER: HD iPSC Consortium 

PROVIDER: S-EPMC5610046 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature