The organization of the transcriptional network in specific neuronal classes
Abstract Genome‐wide expression profiling has aided the understanding of the molecular basis of neuronal diversity, but achieving broad functional insight remains a considerable challenge. Here, we perform the first systems‐level analysis of microarray data from single neuronal populations using wei...
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| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Springer Nature
2009-07-01
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| Series: | Molecular Systems Biology |
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| Online Access: | https://doi.org/10.1038/msb.2009.46 |
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| _version_ | 1849225794100920320 |
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| author | Kellen D Winden Michael C Oldham Karoly Mirnics Philip J Ebert Christo H Swan Pat Levitt John L Rubenstein Steve Horvath Daniel H Geschwind |
| author_facet | Kellen D Winden Michael C Oldham Karoly Mirnics Philip J Ebert Christo H Swan Pat Levitt John L Rubenstein Steve Horvath Daniel H Geschwind |
| author_sort | Kellen D Winden |
| collection | DOAJ |
| description | Abstract Genome‐wide expression profiling has aided the understanding of the molecular basis of neuronal diversity, but achieving broad functional insight remains a considerable challenge. Here, we perform the first systems‐level analysis of microarray data from single neuronal populations using weighted gene co‐expression network analysis to examine how neuronal transcriptome organization relates to neuronal function and diversity. We systematically validate network predictions using published proteomic and genomic data. Several network modules of co‐expressed genes correspond to interneuron development programs, in which the hub genes are known to be critical for interneuron specification. Other co‐expression modules relate to fundamental cellular functions, such as energy production, firing rate, trafficking, and synapses, suggesting that fundamental aspects of neuronal diversity are produced by quantitative variation in basic metabolic processes. We identify two transcriptionally distinct mitochondrial modules and demonstrate that one corresponds to mitochondria enriched in neuronal processes and synapses, whereas the other represents a population restricted to the soma. Finally, we show that galectin‐1 is a new interneuron marker, and we validate network predictions in vivo using Rgs4 and Dlx1/2 knockout mice. These analyses provide a basis for understanding how specific aspects of neuronal phenotypic diversity are organized at the transcriptional level. |
| format | Article |
| id | doaj-art-c5a330e753914c15ba2461ae3270b95b |
| institution | Kabale University |
| issn | 1744-4292 |
| language | English |
| publishDate | 2009-07-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | Molecular Systems Biology |
| spelling | doaj-art-c5a330e753914c15ba2461ae3270b95b2025-08-24T11:59:26ZengSpringer NatureMolecular Systems Biology1744-42922009-07-015111810.1038/msb.2009.46The organization of the transcriptional network in specific neuronal classesKellen D Winden0Michael C Oldham1Karoly Mirnics2Philip J Ebert3Christo H Swan4Pat Levitt5John L Rubenstein6Steve Horvath7Daniel H Geschwind8Interdepartmental Program for Neuroscience, University of California Los AngelesInterdepartmental Program for Neuroscience, University of California Los AngelesDepartment of Psychiatry, Vanderbilt UniversityDepartment of Pharmacology, Vanderbilt UniversityDepartment of Psychiatry and Langley Porter Psychiatric Institute, University of CaliforniaVanderbilt Kennedy Center for Research on Human Development, Vanderbilt UniversityDepartment of Psychiatry and Langley Porter Psychiatric Institute, University of CaliforniaDepartment of Human Genetics, University of California Los AngelesInterdepartmental Program for Neuroscience, University of California Los AngelesAbstract Genome‐wide expression profiling has aided the understanding of the molecular basis of neuronal diversity, but achieving broad functional insight remains a considerable challenge. Here, we perform the first systems‐level analysis of microarray data from single neuronal populations using weighted gene co‐expression network analysis to examine how neuronal transcriptome organization relates to neuronal function and diversity. We systematically validate network predictions using published proteomic and genomic data. Several network modules of co‐expressed genes correspond to interneuron development programs, in which the hub genes are known to be critical for interneuron specification. Other co‐expression modules relate to fundamental cellular functions, such as energy production, firing rate, trafficking, and synapses, suggesting that fundamental aspects of neuronal diversity are produced by quantitative variation in basic metabolic processes. We identify two transcriptionally distinct mitochondrial modules and demonstrate that one corresponds to mitochondria enriched in neuronal processes and synapses, whereas the other represents a population restricted to the soma. Finally, we show that galectin‐1 is a new interneuron marker, and we validate network predictions in vivo using Rgs4 and Dlx1/2 knockout mice. These analyses provide a basis for understanding how specific aspects of neuronal phenotypic diversity are organized at the transcriptional level.https://doi.org/10.1038/msb.2009.46developmentmicroarraymitochondrianeuronal diversitysystems biology |
| spellingShingle | Kellen D Winden Michael C Oldham Karoly Mirnics Philip J Ebert Christo H Swan Pat Levitt John L Rubenstein Steve Horvath Daniel H Geschwind The organization of the transcriptional network in specific neuronal classes Molecular Systems Biology development microarray mitochondria neuronal diversity systems biology |
| title | The organization of the transcriptional network in specific neuronal classes |
| title_full | The organization of the transcriptional network in specific neuronal classes |
| title_fullStr | The organization of the transcriptional network in specific neuronal classes |
| title_full_unstemmed | The organization of the transcriptional network in specific neuronal classes |
| title_short | The organization of the transcriptional network in specific neuronal classes |
| title_sort | organization of the transcriptional network in specific neuronal classes |
| topic | development microarray mitochondria neuronal diversity systems biology |
| url | https://doi.org/10.1038/msb.2009.46 |
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