Secretome Analysis of Human Oligodendrocytes Derived from Neural Stem Cells

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.

Astrocyte and Oligodendrocyte Cross-Talk in the Central Nervous System

“…In mice, administration of cuprizone, that damages and ablates oligodendrocytes, both oligodendrocytes and OPCs secrete IL-1β, a known pro-inflammatory cytokine [90][91][92]. CXCL1, CXCL2, CXCL3, CXCL5, and CXCL6 all bind the CXCR2 receptor, which is constitutively expressed on oligodendrocytes, but not present on astrocytes [88,93]. The CXCR2 receptor is upregulated in response to these cytokines that are secreted by oligodendrocytes, supporting autocrine regulation.…”

“…Several CXCR2 ligands have previously been associated with OPC proliferation and differentiation [94], indicating that oligodendrocytes regulate their own proliferation. Granulocyte macrophage colony stimulating factor (GM-CSF) is upregulated in resting oligodendrocytes [93] which has been found to be anti-apoptotic for neurons and neuroprotective in models of stroke. Additionally, astrocytes secrete CXCL1 in spinal cord injury and in MS lesions, both in vivo and in vitro, which may act to recruit oligodendrocytes [88,95].…”

Laminins and their receptors in the CNS

“…Oligodendrocytes are glial cells responsible for the myelination of neurons in the CNS (Bradl & Lassmann, 2010). Recently, a secretome analysis demonstrated that oligodendrocytes were able to synthesize various laminin chains, including α2, α4, α5, β1, β2, β3, γ 1 and γ 2 (Kim et al, 2014), suggesting that these cells are able to generate most laminin isoforms. The exact laminin isoforms synthesized by oligodendrocytes, however, remain unknown.…”

Survival and Functionality of Human Induced Pluripotent Stem Cell-Derived Oligodendrocytes in a Nonhuman Primate Model for Multiple Sclerosis

“…In addition, neuroprotective effects of the secretome of NSCs have been demonstrated after spinal cord injury in mice [21] and after intracerebellar injection of NSCs in mouse models of Machado-Joseph disease [28]. The responsible factors in the secretome of NSCs and OPCs have been determined [22,[29][30][31]. Also in this study, human iPSC-derived OPCs appeared to express a similar set of factors and were able to reduce the EAE clinical score in mice after intraventricular injection, mainly by reducing cell infiltration and lesion size.…”