3D cultured human medium spiny neurons functionally integrate and rescue motor deficits in Huntington's disease mice.

ABSTRACT: Dysfunction of striatal medium spiny neurons (MSNs) is implicated in several neurological disorders, including Huntington's disease (HD). Despite progress in characterizing MSN pathology in HD, mechanisms underlying MSN susceptibility remain unknown, driving the need for MSNs derived from human pluripotent stem cells (hPSCs), especially subtypes in research and therapy. Here, we established a scalable 3D-default culture system to produce striatal MSNs efficiently from hPSCs by activation of the endogenous sonic hedgehog (SHH) pathway. These cells expressed canonical markers of striatal progenitors and dopamine D1 (D1) and dopamine D2 (D2) MSNs and presented dynamic specification and transcriptional signatures that closely resemble endogenous MSNs at single-cell resolution, both in vitro an

SUBMITTER: Mei Y 

PROVIDER: S-EPMC12520685 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature