摘要
The 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 astrocytederived 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 TGFβsignaling 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.
基金
This work was supported in part by research grants from the State Key Program of the National Natural Science Foundation of China(No.81830037 to J.Z.)
the National Basic Research Program of China(973 Program Grant No.2014CB965001 to JZ)
Innovative Research Groups of the National Natural Science Foundation of China(No.81221001 to JZ)
Joint Research Fund for Overseas Chinese,Hong Kong and Macao Young Scientists of the National Natural Science Foundation of China(No.81329002 to JZ)
the National Institutes of Health(No.1R01NS097195–01 to JZ)
the National Natural Science Foundation of China(No.81901333 to XX)
Shanghai Sailing Program(No.19YF1451700 to XX)
China Postdoctoral Science Foundation Grant(No.2018 M642087 to XX).
