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Astrocyte proximity modulates the myelination gene fabric of oligodendrocytes

Published online by Cambridge University Press:  05 January 2011

Sanda Iacobas
Affiliation:
Neuroscience, Albert Einstein College of Medicine, New York, USA
Dumitru A. Iacobas*
Affiliation:
Neuroscience, Albert Einstein College of Medicine, New York, USA
*
Correspondence should be addressed to: Dumitru A. Iacobas, D.P. Purpura Department of Neuroscience, Kennedy Center, Room No. 713, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx-New York, NY 10461, USA phone: (718) 430-3326 fax: (718) 430-8594 email: dumitru.iacobas@einstein.yu.edu

Abstract

Extensive literature documented that astrocytes release neurotransmitters, cytokines and other signaling molecules to 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 co-cultured with non-touching astrocytes we found profound changes in the 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 dibutyryl-cAMP (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 the enhancer of zeste homolog 2 as the most relevant MYE gene in the astrocyte proximity, notch gene homolog 1 in control and B-cell leukemia/lymphoma 2 in differentiated Oli-neu cells.

Type
Research Article
Copyright
Copyright © Cambridge University Press 2010

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