Unknown

Dataset Information

0

Network-Based Genomic Analysis of Human Oligodendrocyte Progenitor Differentiation.


ABSTRACT: 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 PDGF?R+ 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 ?4 (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.

SUBMITTER: Pol SU 

PROVIDER: S-EPMC5550273 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

altmetric image

Publications

Network-Based Genomic Analysis of Human Oligodendrocyte Progenitor Differentiation.

Pol Suyog U SU   Polanco Jessie J JJ   Seidman Richard A RA   O'Bara Melanie A MA   Shayya Hani J HJ   Dietz Karen C KC   Sim Fraser J FJ  

Stem cell reports 20170801 2


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<sup>+</sup> hOPCs during initial oligodendrocyte commitment. Weighted gene coexpression network analysis was used to define progenitor and differentiation-specific gene expres  ...[more]

Similar Datasets

| S-EPMC6674672 | biostudies-literature
| S-EPMC4104854 | biostudies-literature
| S-EPMC3728712 | biostudies-literature
| S-EPMC7060805 | biostudies-literature
| S-EPMC5574064 | biostudies-literature
| S-EPMC6614186 | biostudies-literature
| S-EPMC3715795 | biostudies-literature
| S-EPMC5132073 | biostudies-literature
| S-EPMC9007940 | biostudies-literature
| S-EPMC2034312 | biostudies-literature