2026-07-03 理化学研究所
病（la Maladie）に抗う生命の華（les Fleurs）ように見えるHD脳での遺伝子ネットワーク
＜関連情報＞
- https://www.riken.jp/press/2026/20260703_2/index.html
- https://www.nature.com/articles/s41598-026-56101-8
ハンチントン病患者の脳における遺伝子発現のトポロジーモデリングにより、共発現ネットワークの選択的破壊が明らかになった Topological modeling of gene expression in the brain with Huntington’s disease reveals selective disruption of co-expression network
Yuko Okamura-Oho,Kazuro Shimokawa,Satoshi Oota,Atsushi Yoshiki,Masahiko Morita,Masaomi Nishimura,Sakiko Nakamura,Yuki Tsujimura,Shumpei Ishikawa & Hideo Yokota
Scientific Reports Published:30 June 2026
DOI:https://doi.org/10.1038/s41598-026-56101-8
Abstract
We applied transcriptome tomography to create a whole-brain model of early-stage Huntington’s disease (HD) in R6/2 mice, which ubiquitously express truncated human mutant HTT containing approximately 150 CAG repeats. Medium spiny neuron (MSN)-related genes showed abnormal expression in the HD brain, in terms of expression similarity to wild-type Htt. Bdnf was the most probable upstream regulator of these genes. Smarca4, the Bdnf-regulator, was similarly expressed to wild-type Htt in the control brain; however, this was not observed in HD, implying a possible involvement of Smarca4 in glutamate excitotoxicity in HD. Lhx6, a master gene for MSN-related pathway development ordinarily conserved postnatally and in adulthood, was lost in the HD co-expression network. And a network hub node, Fcho1, was lost in connection involving Lhx6 and mitochondrial gene clusters. Loss of Smarca4, Lhx6, and Fcho1 in co-expression may contribute to spatiotemporally specific neuronal loss in HD.
