Reprogrammed astrocytes display higher neurogenic competence, migration ability and cell death resistance than reprogrammed fibroblasts

Abstract

AbstractThe direct reprogramming of somatic cells into induced neural progenitor cells (iNPCs) has been envisioned as a promising approach to overcome ethical and clinical issues of pluripotent stem cell transplantation. We previously reported that astrocyte-derived induced pluripotent stem cells (iPSCs) have more tendencies for neuronal differentiation than fibroblast-derived iPSCs. However, the differences of neurogenic potential between astrocyte-derived iNPCs (AiNPCs) and iNPCs from non-neural origins, such as fibroblast-derived iNPCs (FiNPCs), and the underlying mechanisms remain unclear. Our results suggested that AiNPCs exhibited higher differentiation efficiency, mobility and survival capacities, compared to FiNPCs. The whole transcriptome analysis revealed higher activities of TGFβ signaling in AiNPCs, versus FiNPCs, following a similar trend between astrocytes and fibroblasts. The higher neurogenic competence, migration ability, and cell death resistance of AiNPCs could be abrogated using TGFβ signaling inhibitor LY2157299. Hence, our study demonstrates the difference between iNPCs generated from neural and non-neural cells, together with the underlying mechanisms, which, provides valuable information for donor cell selection in the reprogramming approach.