英国剑桥大学Richard Dear等研究人员发现，皮层基因表达结构将健康神经发育与自闭症和精神分裂症的成像、转录组学和遗传学联系起来。相关论文于2024年4月22日在线发表在《自然—神经科学》杂志上。

研究人员对艾伦人脑图谱的优化处理揭示了大脑皮层基因表达结构的两个新成分——C2 和 C3，它们明显富集于神经元、代谢和免疫过程、特定细胞类型和细胞结构，以及与智力相关的基因变异。利用其他数据集（PsychENCODE、Allen Cell Atlas和BrainSpan），研究人员发现C1-C3代表了可通用的转录程序，这些程序在细胞内协调进行，并在胎儿和出生后的发育过程中分阶段进行。

在神经影像学、差异表达和全基因组关联研究中，自闭症谱系障碍和精神分裂症分别与C1/C2和C3特别相关。有证据表明，C3是青少年大脑发育的规范转录程序，可导致精神分裂症高遗传风险人群的非典型超颗粒皮层连接。

研究人员表示，人类大脑组织涉及数千个基因的协调表达。例如，大脑皮层转录的第一个主成分（C1）确定了从感觉运动区到联想区的层次结构。

附：英文原文

Title: Cortical gene expression architecture links healthy neurodevelopment to the imaging, transcriptomics and genetics of autism and schizophrenia

Author: Dear, Richard, Wagstyl, Konrad, Seidlitz, Jakob, Markello, Ross D., Arnatkeviit, Aurina, Anderson, Kevin M., Bethlehem, Richard A. I., Raznahan, Armin, Bullmore, Edward T., Vrtes, Petra E.

Issue&Volume: 2024-04-22

Abstract: Human brain organization involves the coordinated expression of thousands of genes. For example, the first principal component (C1) of cortical transcription identifies a hierarchy from sensorimotor to association regions. In this study, optimized processing of the Allen Human Brain Atlas revealed two new components of cortical gene expression architecture, C2 and C3, which are distinctively enriched for neuronal, metabolic and immune processes, specific cell types and cytoarchitectonics, and genetic variants associated with intelligence. Using additional datasets (PsychENCODE, Allen Cell Atlas and BrainSpan), we found that C1–C3 represent generalizable transcriptional programs that are coordinated within cells and differentially phased during fetal and postnatal development. Autism spectrum disorder and schizophrenia were specifically associated with C1/C2 and C3, respectively, across neuroimaging, differential expression and genome-wide association studies. Evidence converged especially in support of C3 as a normative transcriptional program for adolescent brain development, which can lead to atypical supragranular cortical connectivity in people at high genetic risk for schizophrenia.

DOI: 10.1038/s41593-024-01624-4

Source: https://www.nature.com/articles/s41593-024-01624-4