Functional organization of the transcriptome in human brain

Michael C. Oldham, Genevieve Konopka, Kazuya Iwamoto, Peter Langfelder, Tadafumi Kato, Steve Horvath, Daniel H. Geschwind

Research output: Contribution to journalArticle

434 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1271-1282
Number of pages12
JournalNature Neuroscience
Volume11
Issue number11
DOIs
StatePublished - Nov 2008

Fingerprint

Transcriptome
Brain
Astrocytes
Program Development
Neural Stem Cells
Gene Regulatory Networks
Lateral Ventricles
Oligodendroglia
Microglia
Human Genome
Organelles
Genes
Gene Expression
Neurons
Population

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Oldham, M. C., Konopka, G., Iwamoto, K., Langfelder, P., Kato, T., Horvath, S., & Geschwind, D. H. (2008). Functional organization of the transcriptome in human brain. Nature Neuroscience, 11(11), 1271-1282. https://doi.org/10.1038/nn.2207

Functional organization of the transcriptome in human brain. / Oldham, Michael C.; Konopka, Genevieve; Iwamoto, Kazuya; Langfelder, Peter; Kato, Tadafumi; Horvath, Steve; Geschwind, Daniel H.

In: Nature Neuroscience, Vol. 11, No. 11, 11.2008, p. 1271-1282.

Research output: Contribution to journalArticle

Oldham, MC, Konopka, G, Iwamoto, K, Langfelder, P, Kato, T, Horvath, S & Geschwind, DH 2008, 'Functional organization of the transcriptome in human brain', Nature Neuroscience, vol. 11, no. 11, pp. 1271-1282. https://doi.org/10.1038/nn.2207
Oldham MC, Konopka G, Iwamoto K, Langfelder P, Kato T, Horvath S et al. Functional organization of the transcriptome in human brain. Nature Neuroscience. 2008 Nov;11(11):1271-1282. https://doi.org/10.1038/nn.2207
Oldham, Michael C. ; Konopka, Genevieve ; Iwamoto, Kazuya ; Langfelder, Peter ; Kato, Tadafumi ; Horvath, Steve ; Geschwind, Daniel H. / Functional organization of the transcriptome in human brain. In: Nature Neuroscience. 2008 ; Vol. 11, No. 11. pp. 1271-1282.
@article{0ef1dba2d8f94cb5bfc0314c30e3dd16,
title = "Functional organization of the transcriptome in human brain",
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.",
author = "Oldham, {Michael C.} and Genevieve Konopka and Kazuya Iwamoto and Peter Langfelder and Tadafumi Kato and Steve Horvath and Geschwind, {Daniel H.}",
year = "2008",
month = "11",
doi = "10.1038/nn.2207",
language = "English (US)",
volume = "11",
pages = "1271--1282",
journal = "Nature Neuroscience",
issn = "1097-6256",
publisher = "Nature Publishing Group",
number = "11",

}

TY - JOUR

T1 - Functional organization of the transcriptome in human brain

AU - Oldham, Michael C.

AU - Konopka, Genevieve

AU - Iwamoto, Kazuya

AU - Langfelder, Peter

AU - Kato, Tadafumi

AU - Horvath, Steve

AU - Geschwind, Daniel H.

PY - 2008/11

Y1 - 2008/11

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=54949113578&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=54949113578&partnerID=8YFLogxK

U2 - 10.1038/nn.2207

DO - 10.1038/nn.2207

M3 - Article

VL - 11

SP - 1271

EP - 1282

JO - Nature Neuroscience

JF - Nature Neuroscience

SN - 1097-6256

IS - 11

ER -