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Generation and Expansion of highly-pure Motor Neuron Progenitors from Human Pluripotent Stem Cells

Human pluripotent stem cells (hPSCs) have opened new opportunities for understanding human development, modeling disease processes and developing new therapeutics. However, these applications are hindered by low-efficiency and heterogeneity of target cell types differentiated from hPSCs, such as mot...

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Detalles Bibliográficos
Autores principales: Du, Zhong-Wei, Chen, Hong, Liu, Huisheng, Lu, Jianfeng, Qian, Kun, Huang, Cindy Tzu-Ling., Zhong, Xiaofen, Fan, Frank, Zhang, Su-Chun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4375778/
https://www.ncbi.nlm.nih.gov/pubmed/25806427
http://dx.doi.org/10.1038/ncomms7626
Descripción
Sumario:Human pluripotent stem cells (hPSCs) have opened new opportunities for understanding human development, modeling disease processes and developing new therapeutics. However, these applications are hindered by low-efficiency and heterogeneity of target cell types differentiated from hPSCs, such as motor neurons (MNs), as well as our inability to maintain the potency of lineage committed progenitors. Here, by using a combination of small molecules that regulate multiple signaling 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 5 passages so that a single MNP can be amplified to 1×10(4). This method is reproducible in human induced pluripotent stem cells and is applied to model MNdegenerative diseases and in proof-of-principle drug screening assays.