Article abstract


Nature Neuroscience 11, 1271 - 1282 (2008)
Published online: 12 October 2008 | doi:10.1038/nn.2207

Functional organization of the transcriptome in human brain

Michael C Oldham1,2, Genevieve Konopka2, Kazuya Iwamoto3, Peter Langfelder4, Tadafumi Kato3, Steve Horvath4,5,6 & Daniel H Geschwind2,4,6


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.

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  1. Interdepartmental Program for Neuroscience, University of California Los Angeles, 695 Charles Young Drive South, Gonda Room 1506D, Los Angeles, California 90095, USA.
  2. Program in Neurogenetics, Department of Neurology, and the Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California Los Angeles, 710 Westwood Plaza, Los Angeles, California 90095, USA.
  3. Laboratory for Molecular Dynamics of Mental Disorders, RIKEN Brain Science Institute, Hirosawa 2-1, Wako, Saitama 351-0198, Japan.
  4. Department of Human Genetics, University of California Los Angeles, 695 Charles Young Drive South, Gonda Room 6357, Los Angeles, California 90095, USA.
  5. Department of Biostatistics, University of California Los Angeles School of Public Health, 650 Charles Young Drive South, Los Angeles, California 90095, USA.
  6. These authors contributed equally to this work.

Correspondence to: Michael C Oldham1,2 e-mail: oldham@ucla.edu

Correspondence to: Daniel H Geschwind2,4,6 e-mail: dhg@ucla.edu



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