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Nat Commun. 2015 Mar 25;6:6626. doi: 10.1038/ncomms7626.

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

Author information

1
Waisman Center, University of Wisconsin, Madison, Wisconsin 53705, USA.
2
1] Waisman Center, University of Wisconsin, Madison, Wisconsin 53705, USA [2] Department of Rehabilitation Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
3
1] Waisman Center, University of Wisconsin, Madison, Wisconsin 53705, USA [2] Reproductive Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
4
Promega Corporation, Madison, Wisconsin 53711, USA.
5
1] Waisman Center, University of Wisconsin, Madison, Wisconsin 53705, USA [2] Department of Neuroscience and Department of Neurology, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin 53705, USA.

Abstract

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 × 10(4). 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.

PMID:
25806427
PMCID:
PMC4375778
DOI:
10.1038/ncomms7626
[Indexed for MEDLINE]
Free PMC Article

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