Network-Based Genomic Analysis of Human Oligodendrocyte Progenitor Differentiation
| Autor: | Karen C. Dietz, Jessie J. Polanco, Richard A. Seidman, Suyog Pol, Fraser J. Sim, Melanie A. O'Bara, Hani J. Shayya |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Resource Rodentia Biology Biochemistry Receptors G-Protein-Coupled 03 medical and health sciences Myelin RAG2 Gene expression Genetics medicine Animals Humans Gene Regulatory Networks Remyelination Gene lcsh:QH301-705.5 Progenitor Oligodendrocyte Precursor Cells lcsh:R5-920 species conservation Gene Expression Profiling GTP-Binding Protein beta Subunits Oligodendrocyte differentiation Computational Biology Cell Differentiation Cell Biology Genomics Oligodendrocyte Axons Cell biology Oligodendroglia 030104 developmental biology medicine.anatomical_structure Gene Expression Regulation lcsh:Biology (General) Transcriptome lcsh:Medicine (General) Developmental Biology oligodendrocyte progenitor Signal Transduction |
| Zdroj: | Stem Cell Reports, Vol 9, Iss 2, Pp 710-723 (2017) Stem Cell Reports |
| ISSN: | 2213-6711 |
| Popis: | Summary Impaired human oligodendrocyte progenitor cell (hOPC) differentiation likely contributes to failed remyelination in multiple sclerosis. The characterization of molecular pathways that regulate hOPC differentiation will provide means to induce remyelination. In this study, we determined the gene expression profile of PDGFαR+ hOPCs during initial oligodendrocyte commitment. Weighted gene coexpression network analysis was used to define progenitor and differentiation-specific gene expression modules and functionally important hub genes. These modules were compared with rodent OPC and oligodendrocyte data to determine the extent of species conservation. These analyses identified G-protein β4 (GNB4), which was associated with hOPC commitment. Lentiviral GNB4 overexpression rapidly induced human oligodendrocyte differentiation. Following xenograft in hypomyelinating shiverer/rag2 mice, GNB4 overexpression augmented myelin synthesis and the ability of hOPCs to ensheath host axons, establishing GNB4 as functionally important in human myelination. As such, network analysis of hOPC gene expression accurately predicts genes that influence human oligodendrocyte differentiation in vivo. Highlights • Transcriptional database of differentiating human oligodendrocyte progenitor cells • WGCNA reveals coordinated gene networks in oligodendrocyte specification • Dataset comparison identifies unique and shared cross-species gene networks • G-protein β4 (GNB4) expression accelerates human oligodendrocyte differentiation Oligodendrocyte progenitor cell differentiation requires the coordinated regulation of many genes. Sim and colleagues capture the transcriptional profile during human primary oligodendrocyte specification. Using WGCNA and cross-species dataset comparisons, they identify jointly regulated genes, conserved across human and rodent species. Targeting highly regulated genes, they show that G-protein subunit β4 expression accelerates human oligodendrocyte differentiation. |
| Databáze: | OpenAIRE |
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