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Generation and expansion of highly pure motor neuron progenitors from human pluripotent stem cells

2015; Nature Portfolio; Volume: 6; Issue: 1 Linguagem: Inglês

10.1038/ncomms7626

2041-1723

Zhongwei Du, Hong Chen, Huisheng Liu, Jianfeng Lü, Kun Qian, CindyTzu-Ling Huang, Xiaofen Zhong, Frank Fan, Su‐Chun Zhang,

RNA Interference and Gene Delivery

Human pluripotent stem cells (hPSCs) have opened new opportunities for understanding human development, modelling disease processes and developing new therapeutics. However, these applications are hindered by the low efficiency and heterogeneity of cell types, such as motorneurons (MNs), differentiated from hPSCs as well as our inability to maintain the potency of lineage-committed progenitors. Here by using a combination of small molecules that regulate multiple signalling pathways, we develop a method to guide human embryonic stem cells to a near-pure population (>95%) of motor neuron progenitors (MNPs) in 12 days, and an enriched population (>90%) of functionally mature MNs in an additional 16 days. More importantly, the MNPs can be expanded for at least five passages so that a single MNP can be amplified to 1 × 104. This method is reproducible in human-induced pluripotent stem cells and is applied to model MN-degenerative diseases and in proof-of-principle drug-screening assays. Applications of human pluripotent stem cells (hPSCs) for disease modelling or cell therapy are hindered by low efficiency and heterogeneity of target cell types differentiated from hPSCs, such as motor neurons (MNs). Here the authors develop a method to derive highly pure motor neuron progenitor populations from human embryonic and induced pluripotent stem cells that yield functional MNs.