Intersecting impact of CAG repeat and huntingtin knockout in stem cell-derived cortical neurons.

ABSTRACT: Huntington's Disease (HD) is caused by a CAG repeat expansion in the gene encoding huntingtin (HTT). While normal HTT function appears impacted by the mutation, the specific pathways unique to CAG repeat expansion versus loss of normal function are unclear. To understand the impact of the CAG repeat expansion, we evaluated biological signatures of HTT knockout (HTT KO) versus those that occur from the CAG repeat expansion by applying multi-omics, live cell imaging, survival analysis and a novel feature-based pipeline to study cortical neurons (eCNs) derived from an isogenic human embryonic stem cell series (RUES2). HTT KO and the CAG repeat expansion influence developmental trajectories of eCNs, with opposing effects on growth. Network analyses of differentially expressed genes and protein

SUBMITTER: Stocksdale JT 

PROVIDER: S-EPMC12668206 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature