Abstract
In this study, we investigated the secretome of human oligodendrocytes (F3.Olig2 cells) generated from human neural stem cells by transduction with the gene encoding the Olig2 transcription factor. Using mRNA sequencing and protein cytokine arrays, we identified a number of biologically important secretory proteins whose expression has not been previously reported in oligodendrocytes. We found that F3.Olig2 cells secrete IL-6, PDGF-AA, GRO, GM-CSF, and M-CSF, and showed prominent expression of their corresponding receptors. Co-expression of ligands and receptors suggests that autocrine signaling loops may play important roles in both differentiation and maintenance of oligodendrocytes. We also found that F3.Olig2 cells secrete matrix metalloproteinases and matrix metalloproteinase-associated proteins associated with functional competence of oligodendrocytes. The results of our secretome analysis provide insights into the functional and molecular details of human oligodendrocytes. To the best of our knowledge, this is the first systematic analysis of the secretome of oligodendrocytes.
Highlights
In the central nervous system (CNS), oligodendrocytes form the myelin sheath that electrically insulates axons [1,2]
We characterized the secretome of human oligodendrocytes derived from human neural stem cells (NSCs)
This study was performed to characterize the secretome of F3.Olig2 cells, human oligodendrocytes derived from human NSCs, in order to gain insight into the functional and molecular details of human oligodendrocytes
Summary
In the central nervous system (CNS), oligodendrocytes form the myelin sheath that electrically insulates axons [1,2]. Loss of oligodendrocytes results in demyelination and subsequent axonal degeneration [3,4,5,6], for which there are currently no effective therapies [7]. Despite their biological importance, oligodendrocytes have not been extensively characterized at the molecular level, partly because it is challenging to harvest oligodendrocytes from the brain, either directly or indirectly through primary culture. The secretome of oligodendrocytes has not been studied in the past, due to the limited availability of purified populations of CNS cell types such as neurons, astrocytes, and oligodendrocytes. We have recently established a pure population of human oligodendrocytes generated by transducing human NSCs with the gene encoding the oligodendrocytes-specific transcription factor Olig; the resultant cells have the characteristics of mature human oligodendrocytes [15,16]
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