Unknown,Transcriptomics,Genomics,Proteomics

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Direct genesis of functional rodent and human Schwann cells from skin mesenchymal precursors (rat)

ABSTRACT: Recent reports of directed reprogramming have raised questions about the stability of cell lineages. Here, we have addressed this issue, focusing upon skin-derived precursors (SKPs), a dermally-derived precursor cell. We show by lineage tracing that murine SKPs from dorsal skin originate from mesenchymal and not neural crest-derived cells. These mesenchymally-derived SKPs can, without genetic manipulation, generate functional Schwann cells, a neural crest cell type, and are highly similar at the transcriptional level to Schwann cells isolated from the peripheral nerve. This is not a mouse-specific phenomenon, since human SKPs that are highly similar at the transcriptome level can be made from facial (neural crest-derived) and foreskin (mesodermally-derived) dermis, and the mesodermally-derived SKPs can make myelinating Schwann cells. Thus, non-neural crest-derived mesenchymal precursors can differentiate into bona fide peripheral glia in the absence of genetic manipulation, suggesting that developmentally-defined lineage boundaries are more flexible than widely thought. We obtained 3 independent samples of nerve Schwann cells, SKP-derived Schwann cells, and Dorsal Trunk SKPs, each, from adult SD rats. Primary cells were isolated and cultured, and RNA was collected from those cultured samples. RNA samples deriving from these cells were analyzed on the Affymetrix Rat Gene 1.0 ST Array.

ORGANISM(S): Rattus norvegicus

SUBMITTER: Freda Miller

PROVIDER: E-GEOD-57505 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:The current understanding is that Schwann cell transplantation is ideal strategy for peripheral nerve regeneration instead of autograft. It is difficult to obtain the required amount of Schwann cells which are best transplant condition, and central nervous cells have been gained attention in recent years, but its regenerative mechanism remain unknown. Neural stem/progenitor cells (NSPC) can generate various type of neural lineage cells (NLCs), and NSPCs derived from pluripotent stem cells are promising cells for cell therapy for neurodegenerative diseases. However, more safe and accessible cell source of NSPCs are required. In this study, we aim to provide NLCs derived from human dental pulp stem cells (DPSCs), and reveal the mechanism involved in regeneration after NLCs transplantation into peripheral nerve defect. Here, characterization of NLCs, paracrine effects for endothelial cells and Schwann cells, in xenotransplant for rat 10mm sciatic nerve defect, the differentiation, the survival, and outcome of nerve regeneration were investigated. Induced NLCs consisted of neuronal lineage cells, astrocyte lineage cells, oligodendrocyte lineage cells, and neural crest lineage cells. Considering retrospectively, NLCs were possible derived from NSPCs. Microarray analysis revealed neural markers of primary embryological development were up-regulated in induced NLCs compared to DPSCs. Moreover, NLCs enhanced the activity of endothelial cells and Schwann cells by paracrine effects in vitro. Two weeks after transplantation, many transplanted NLCs differentiated into platelet-derived growth factor receptor alpha (PDGFRa) + oligodendrocyte progenitor cells (OPCs), and PDGFRa+/p75 neurotrophin receptor + Schwann cells derived from OPCs were observed. Twelve weeks after transplantation, NLCs promoted functional repair of peripheral nerve. A few human Schwann cells survived, but did not myelinate axon. These findings suggest that some of mechanism promoting for peripheral nerve regeneration by transplanted NLCs. Transplantation of NLCs derived from DPSCs into partial peripheral nerve defect may be widely used for further experiments.