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May 8, 2026Stem Cells

Huntington’s Disease Human Lateral Ganglionic Eminence Precursors Differentiate into Functionally Mature Medium Spiny Neurons Exhibiting Pathology

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Authors

AMAmy McCaughey‐ChapmanBCBronwen Connor

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Overview

Randomized trial demonstrates differentiation of lateral ganglionic eminence precursors into pathological neurons in Huntington’s disease, suggesting potential therapeutic pathways.

Key Points

  • To investigate if direct reprogramming of fibroblasts can generate functional medium spiny neurons (MSNs) representing Huntington's disease pathology.
  • Derived human induced lateral ganglionic eminence precursors (hiLGEP) from normal and HD fibroblasts via direct reprogramming.
  • Differentiated hiLGEPs into medium spiny neurons (MSNs) and compared gene and protein expression.
  • Assessed the synaptic functionality using live cell calcium imaging.
  • hiLGEPs from HD fibroblasts show abnormal expression of FOXP1 and FOXP2 and exhibit pathological features indicative of HD.
  • MSNs derived from HD hiLGEPs have reduced expression of several neurotrophic factors, exhibit MW8+ mHTT aggregates, and display morphological abnormalities.
  • 100 µM dopamine was required to elicit a calcium response from HD-derived MSNs, indicating altered synaptic functionality.

Cite This Study

McCaughey‐Chapman et al. (2026) studied this question.

synapsesocial.com/papers/69fd8021bfa21ec5bbf088cdhttps://doi.org/10.1093/stmcls/sxag025
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Rapid and high-purity differentiation of human medium spiny neurons reveals LMNB1 hypofunction and subtype necessity in modeling Huntington’s disease2024 · 5 citations
  2. 2Patient-derived neuron model: Capturing age-dependent adult-onset degenerative pathology in Huntington’s disease2024 · 4 citations
  3. 3Transplanted human striatal progenitors exhibit functional integration and modulate host circuitry in a Huntington’s disease animal model2025
  4. 4Direct reprogramming of somatic skin cells from a patient with Huntington's disease into striatal neurons to create models of pathology2024
  5. 5Clinical-Grade Human Induced Pluripotent Stem Cell-Derived Neural Precursor Cells Restore Motor Function and Preserve Striatal Integrity in a Quinolinic Acid-Lesioned Rat Model of Huntington's Disease.2026