Oldham Michael C, Konopka Genevieve, Iwamoto Kazuya, Langfelder Peter, Kato Tadafumi, Horvath Steve, Geschwind Daniel H
Interdepartmental Program for Neuroscience, University of California Los Angeles, Los Angeles, California 90095, USA.
Nat Neurosci. 2008 Nov;11(11):1271-82. doi: 10.1038/nn.2207. Epub 2008 Oct 12.
The enormous complexity of the human brain ultimately derives from a finite set of molecular instructions encoded in the human genome. These instructions can be directly studied by exploring the organization of the brain's transcriptome through systematic analysis of gene coexpression relationships. We analyzed gene coexpression relationships in microarray data generated from specific human brain regions and identified modules of coexpressed genes that correspond to neurons, oligodendrocytes, astrocytes and microglia. These modules provide an initial description of the transcriptional programs that distinguish the major cell classes of the human brain and indicate that cell type-specific information can be obtained from whole brain tissue without isolating homogeneous populations of cells. Other modules corresponded to additional cell types, organelles, synaptic function, gender differences and the subventricular neurogenic niche. We found that subventricular zone astrocytes, which are thought to function as neural stem cells in adults, have a distinct gene expression pattern relative to protoplasmic astrocytes. Our findings provide a new foundation for neurogenetic inquiries by revealing a robust and previously unrecognized organization to the human brain transcriptome.
人类大脑的极端复杂性最终源于人类基因组中编码的一组有限的分子指令。通过对基因共表达关系进行系统分析来探索大脑转录组的组织，可直接研究这些指令。我们分析了从特定人类脑区生成的微阵列数据中的基因共表达关系，并鉴定出与神经元、少突胶质细胞、星形胶质细胞和小胶质细胞相对应的共表达基因模块。这些模块对区分人类大脑主要细胞类型的转录程序进行了初步描述，并表明无需分离细胞的同质群体，就能从全脑组织中获得细胞类型特异性信息。其他模块对应于其他细胞类型、细胞器、突触功能、性别差异以及脑室下神经源性微环境。我们发现，被认为在成体中起神经干细胞作用的脑室下区星形胶质细胞，相对于原浆性星形胶质细胞具有独特的基因表达模式。我们的发现揭示了人类大脑转录组中一个强大且此前未被认识的组织，为神经遗传学研究提供了新的基础。
