Astrocyte proximity modulates the myelination gene fabric of oligodendrocytes. Mus musculus

Extensive literature documented that astrocytes release neurotransmitters, cytokines and other signaling molecules that modulate migration, maturation and myelin synthesis of oligodendrocytes through mechanisms primarily converging on cytosolic [Ca2+] transients. Considering the long term effects, it is expected that astrocyte conditioned medium is a major regulator of gene expression in oligodendrocytes even in the absence of cytosol-to-cytosol communication via astrocyte-oligodendrocyte gap junction channels. Indeed, by comparing the transcriptomes of immortalized precursor oligodendrocyte (Oli-neu) cells when cultured alone and cocultured with non-touching astrocytes we found profound changes in gene expression level, control and networking. Remarkably, the astrocyte proximity was more effective in remodeling the myelination (MYE) gene fabric and its control by cytokine receptor (CYR) modulated intercellular Ca2+-signaling (ICS) transcriptomic network than the db-cAMP treatment induced transformation into myelin-associated glycoprotein-positive oligodendrocyte-like cells. Moreover, astrocyte proximity up-regulated 37 MYE genes and switched on another 14 MYE, 23 ICS and 4 CYR genes, enhancing the roles of the leukemia inhibitory factor receptor and connexins Cx29 and Cx47. The novel Prominent Gene Analysis identified enhancer of zeste homolog 2 as the most relevant MYE gene in the astrocyte proximity, notch gene homolog1 in control and B-cell leukemia/lymphoma 2 in differentiated Oli-neu cells. Overall design: Determine the modifications of the myelination transcriptome induced in Oli- neu control cells by differentiating treatment and proximity of cortical astrocytes. Four culture dishes of each of control, differentiated and in the astrocyte proximity Oli-neu cells were profiled using Duke mouse 30K and 36k oligonucleotide arrays in the "multiple yellow" hybrization design.