The human Schwann cell transcriptome: species-specificity, long-term stability and changes with differentiation

Abstract

Cultured Schwann cells of human origin differ from those isolated from experimental animals in both phenotype and function. However, the basis for this divergence and its significance to potential clinical applications of the primary cells are not fully understood. In this study, we used RNA-seq to comprehensively analyze the human Schwann cell transcriptome and compare it to that of ratcells. We also studied the transcriptomics profiles of human Schwann cells subjected to: (1) the pro-mitogenic effect of growth factors in cells undergoing serial passaging in vitro, and (2) the pro-differentiating action of cAMP, a signal known to promote myelin gene expression in rodent cells.Despite the human Schwann cell transcriptome differedas much as 44% from that of rat Schwann cells established under identical conditions, the human cells maintained their expected Schwann cell identity regardless of sub-culture and the continued influence of mitogenic factors. Strikingly, the transcriptomes of low passage (proliferative) and late passage (senescent) human Schwann cells were essentially undistinguishable with the exception of roughly 100 differentially expressed genes in the senescentpopulations. On the contrary, the human Schwann cell transcriptome was readily and persistently shifted in response to a single treatment with cAMP analogs as highlighted by the >1,300 genes that were upregulated and the >1,700 genes that were downregulated within 1-day post-stimulation. In sum, these results confirmed that human Schwann cellsmaintain their typical gene expression profiles in culture unless challenged with a strong pro-differentiating stimulus. The observed stability of the human Schwann celltranscriptome in the face of expansion and mitogenic stimulation adds a level of safety for theuse of these glial cells in clinical transplantation.