Reprogramming cell fates towards pluripotent stem cells and other cell types has revolutionized our under- standing of cellular plasticity. During the last decade, transcription factors and microRNAs have become power...Reprogramming cell fates towards pluripotent stem cells and other cell types has revolutionized our under- standing of cellular plasticity. During the last decade, transcription factors and microRNAs have become powerful reprogramming factors for modulating cell fates. Recently, many efforts are focused on repro- gramming cell fates by non-viral and non-integrating chemical approaches. Small molecules not only are useful in generating desired cell types in vitro for vari- ous applications, such as disease modeling and cell- based transplantation, but also hold great promise to be further developed as drugs to stimulate patients＇ endogenous cells to repair and regenerate in vivo. Here we will focus on chemical approaches for generating induced pluripotent stem cells, neurons, cardiomy- ocytes, hepatocytes and pancreatic is cells. Significantly, the rapid and exciting advances in cellular reprogramming by small molecules will help us to achieve the long-term goal of curing devastating diseases, injuries, cancers and aging.展开更多
Transplantation of oligodendrocyte progenitor cells (OPCs) is a promising way for treating demyelinating diseases. However, generation of scalable and autologous sources of OPCs has proven difficult. We previously est...Transplantation of oligodendrocyte progenitor cells (OPCs) is a promising way for treating demyelinating diseases. However, generation of scalable and autologous sources of OPCs has proven difficult. We previously established a chemical condition M9 that could specifically initiate neural program in mouse embryonic fibroblasts. Here we found that M9 could induce the formation of colonies that undergo mesenchymal-to-epithelial transition at the early stage of reprogramming. These colonies may represent unstable and neural lineage-restricted intermediates that have not established a neural stem cell identity. By modulating the culture signaling recapitulating the principle of OPC development, these intermediate cells could be reprogrammed towards OPC fate. The chemical-induced OPC-like cells (ciOPLCs) resemble primary neural stem cell-derived OPCs in terms of their morphology, gene expression, and the ability of self-renewal. Upon differentiation, ciOPLCs could produce functional oligodendrocytes and myelinate the neuron axons in vitro, validating their OPC identity molecularly and functionally. Therefore, our study provides a non-integrating approach to OPC reprogramming that may ultimately provide an avenue to patient-specific cell-based or in situ regenerative therapy.展开更多
文摘Reprogramming cell fates towards pluripotent stem cells and other cell types has revolutionized our under- standing of cellular plasticity. During the last decade, transcription factors and microRNAs have become powerful reprogramming factors for modulating cell fates. Recently, many efforts are focused on repro- gramming cell fates by non-viral and non-integrating chemical approaches. Small molecules not only are useful in generating desired cell types in vitro for vari- ous applications, such as disease modeling and cell- based transplantation, but also hold great promise to be further developed as drugs to stimulate patients＇ endogenous cells to repair and regenerate in vivo. Here we will focus on chemical approaches for generating induced pluripotent stem cells, neurons, cardiomy- ocytes, hepatocytes and pancreatic is cells. Significantly, the rapid and exciting advances in cellular reprogramming by small molecules will help us to achieve the long-term goal of curing devastating diseases, injuries, cancers and aging.
基金the Startup Fund from Shanghai Jiao Tong University (SJTU) School of Medicine, the National Natural Science Foundation of China (31771643)Shanghai Pujiang Program (17PJ1405200)the Program for Professor of Special Appointment (Eastern Scholar) at Shanghai Institutions of Higher Learning, Funding from Shanghai Key Laboratory of Reproductive Medicine to M.Z., and S)TU Researcher program for M.Z. and C.L., respectively.
文摘Transplantation of oligodendrocyte progenitor cells (OPCs) is a promising way for treating demyelinating diseases. However, generation of scalable and autologous sources of OPCs has proven difficult. We previously established a chemical condition M9 that could specifically initiate neural program in mouse embryonic fibroblasts. Here we found that M9 could induce the formation of colonies that undergo mesenchymal-to-epithelial transition at the early stage of reprogramming. These colonies may represent unstable and neural lineage-restricted intermediates that have not established a neural stem cell identity. By modulating the culture signaling recapitulating the principle of OPC development, these intermediate cells could be reprogrammed towards OPC fate. The chemical-induced OPC-like cells (ciOPLCs) resemble primary neural stem cell-derived OPCs in terms of their morphology, gene expression, and the ability of self-renewal. Upon differentiation, ciOPLCs could produce functional oligodendrocytes and myelinate the neuron axons in vitro, validating their OPC identity molecularly and functionally. Therefore, our study provides a non-integrating approach to OPC reprogramming that may ultimately provide an avenue to patient-specific cell-based or in situ regenerative therapy.
