Progenitor transcriptional alterations link fetal and adult pathology in Huntington’s disease

Clicks: 16
ID: 333330
2026
Free PDF
Article Quality & Performance Metrics
Overall Quality
Not rated
Combines reader engagement with the AI quality analysis. This article has not been analysed, so there is no overall score — reader engagement is measured and shown alongside.
AI Quality Assessment
Not analyzed
Readership in this journal
Emerging

Ranked #405 of 455 articles by views in Brain research

Most read Least read

Bar heights use a square-root scale. Only the 120 most-read articles are drawn; the journal has 455 in total.

Mint this article as an NFT
Not yet minted

Create a permanent, verifiable on-chain record of this article on the Scimatic Network. The NFT is held in your Journament account, and you can withdraw it to your own wallet at any time.

5 SUSD one-off · no wallet required
Sign in to mint
Abstract
Abstract Huntington’s disease (HD) is an autosomal dominant neurodegenerative disorder caused by a CAG repeat expansion in the HTT gene. Although the mutant huntingtin protein is expressed from conception, clinical symptoms typically emerge in mid-adulthood. Imaging and molecular studies have raised the possibility that HD may involve neurodevelopmental abnormalities, but direct evidence at the single-cell level in the human fetal brain has been lacking. Here we investigated whether early, cell type–specific transcriptional vulnerabilities arise during neurodevelopment, persist into adult pathology, and might be rescued. To address this, we performed single-cell transcriptomic profiling of the lateral ganglionic eminence (LGE) and cortex from a rare, anatomically intact human HD fetal brain, alongside matched controls. These data were complemented by an allelic series of HD mouse embryos and cross-compared with already published human post-mortem brains and brain organoid models’ datasets. Neural progenitors displayed the highest number of differentially expressed genes in the human fetal brain, and were also impacted in the HD mouse model, where additional cell types displayed transcriptional alterations. Notably, human HD progenitor transcriptional signatures were moderately enriched in the developing mouse LGE. These progenitors exhibited increased expression of synaptic pathways coupled with reduced expression of cell maintenance genes. Cross-comparison with publicly available post-mortem HD datasets revealed that components of this transcriptional signature persist into adulthood. Furthermore, cellular interactions were found to mitigate these alterations, highlighting a potentially rescuable fetal-to-adult transcriptional signature with important implications for HD pathogenesis and therapeutic strategies. Together, these findings reinforce the view of HD as a disorder with developmental origins, in which early transcriptional changes may shape neuronal function while increasing susceptibility to later neurodegeneration.
Reference Key
openalex_W7223179762 Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Mattia Battistella, Gianluca Damaggio, Paola Conforti, Andrea Scolz, Simone Maestri, Vittoria Dickinson Bocchi, Davide Iafolla, Maura Galimberti, Marta Morrocchi, Chiara Cordiglieri, Elena Vezzoli, Simona Lodato, Valeria Ranzani, Silvio Viale, Leslie Michels Thompson, Thomas Vogt, Dan Felsenfeld, Jian Chen, Dario Besusso, Elena F. Cattaneo
Are you one of these authors? Claim your profile
Journal Brain research
Year 2026
DOI
10.1093/brain/awag364
URL
https://doi.org/10.1093/brain/awag364
Keywords Keywords not found

Citations

No citations found. To add a citation, contact the admin at info@scimatic.org

Comments

No comments yet. Be the first to comment on this article.