2026-05-01 イェール大学
＜関連情報＞
- https://news.yale.edu/2026/05/01/many-genes-have-been-linked-autism-new-study-suggests-it-may-be-their-path-brain-matters
- https://www.nature.com/articles/s41593-026-02247-7
神経発達障害リスク遺伝子の転写産物および表現型の収束（試験管内および生体内） Transcriptomic and phenotypic convergence of neurodevelopmental disorder risk genes in vitro and in vivo
Meilin Fernandez Garcia,Kayla Retallick-Townsley,April Pruitt,Elizabeth A. Davidson,Novin Balafkan,Jonathan Warrell,Tzu-Chieh Huang,Alfred Kibowen,Zhiyuan Chu,Yi Dai,Sarah E. Fitzpatrick,Ran Meng,Annabel Sen,Sophie Cohen,Olivia Livoti,Suha Khan,Charlotte Becker,Andre Luiz Teles e Silva,Jenny Liu,Grace Dossou,Jen Cheung,Susanna Liu,Sadaf Ghorbani,P. J. Michael Deans,… Kristen Brennand
Nature Neuroscience Published:24 April 2026
DOI:https://doi.org/10.1038/s41593-026-02247-7
Abstract
Diverse risk genes have been identified for neurodevelopmental disorders (NDDs), but how these genes converge on similar biological pathways in neurons, and thus give rise to similar phenotypes, is unclear. Here we apply a pooled CRISPR approach to successfully target 23 NDD loss-of-function genes with roles in chromatin biology and examine convergent effects on gene expression across human induced pluripotent stem cell-derived neural progenitor cells, glutamatergic neurons and GABAergic neurons. Points of convergence vary between these cell types, with the greatest number of convergent genes and strongest convergent networks in mature glutamatergic neurons, where they broadly represent synaptic, epigenetic and, unexpectedly, mitochondrial pathways. The most convergent networks were observed between NDD genes with shared biological annotations, clinical associations and co-expression patterns in human post-mortem brain. Drugs that were predicted to reverse convergent transcriptomic signatures and/or arousal and sensory processing behaviors ameliorated behavioral phenotypes in zebrafish NDD gene mutants. These results suggest that convergent effects of NDD risk genes could provide clinically useful insights.
