皮质基因表达架构将健康的神经发育与自闭症和精神分裂症的成像,转录和遗传学联系起来
Richard Dear1, Konrad Wagstyl2, Jakob Seidlitz3,4,5
1Department of Psychiatry, University of Cambridge, Cambridge, UK. rajd2@cam.ac.uk.
Nature neuroscience
|April 22, 2024
概括
研究人员在人类大脑中发现了新的基因表达模式 (C2和C3),与已知的C1模式不同. 这些模式与大脑发育,智力和神经系统疾病 (如自闭症和精神分裂症) 有关.
科学领域:
- 神经科学是一个神经科学.
- 基因组学就是基因组学.
- 计算生物学 计算生物学
背景情况:
- 人类大脑的组织依赖于复杂的基因表达.
- 皮层转录的第一个主要组成部分 (C1) 反映了传感运动到协会区域的层次结构.
研究的目的:
- 识别皮质基因表达架构的新型组件,超出C1.
- 研究这些成分在发育和疾病方面的作用.
主要方法:
- 优化了艾伦人类大脑图谱的处理.
- 分析额外的数据集,包括PsychENCODE,艾伦细胞地图和BrainSpan.
- 神经成像,差异表达和全基因组关联研究的整合.
主要成果:
- 确定了皮层基因表达的两个新组成部分,C2和C3.
- C2和C3对神经元,代谢,免疫过程,特定细胞类型和与智力相关的遗传变异进行了丰富.
- C1-C3代表具有明显发展阶段的可概括的转录程序.
- 自闭症谱系障碍和精神分裂症分别与C1/C2和C3有关.
- 作为青少年大脑发育的规范性计划,C3有很强的影响,可能会影响精神分裂症风险中的皮质连接.
结论:
- 新的转录程序 (C2,C3) 揭示了人类大脑组织的更深层次.
- 这些程序对正常的大脑发育至关重要,并且与主要的精神疾病有关.
- C3提供了青少年大脑发育和精神分裂症病理生理学的见解.
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