Abstract
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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Acknowledgements
The authors would like to express their gratitude to the individuals who produced and made available to the scientific community the raw data analyzed in this study. Post mortem brain tissue was donated by The Stanley Research Institute's brain collection courtesy of M.B. Knable, E.F. Torrey, M.J. Webster, S. Weis and R.H. Yolken. We are grateful to our colleagues N. Khanlou, J. Pomakian and H. Vinters for their help in obtaining additional post mortem human brain tissue. We also thank C. Wiita for technical support and L. Kawaguchi for administrative support and lab management. This work was supported by the James S. McDonnell Foundation and a Method to Extend Research in Time (MERIT) Award 5R37MH060233 (D.H.G.), funded by the US National Institute of Mental Health.
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M.C.O. designed the study, analyzed the data and wrote the manuscript. S.H. guided data analysis and aided in manuscript preparation. G.K. designed and carried out wet bench experiments. P.L. performed module eigengene network comparisons. K.I. and T.K. provided microarray data. D.H.G. supervised the study, provided funding and aided in manuscript preparation. All authors discussed results and commented on the manuscript.
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Oldham, M., Konopka, G., Iwamoto, K. et al. Functional organization of the transcriptome in human brain. Nat Neurosci 11, 1271–1282 (2008). https://doi.org/10.1038/nn.2207
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DOI: https://doi.org/10.1038/nn.2207
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