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

被引：305

作者：

Du, Zhong-Wei ^{[1
]}

Chen, Hong ^{[1
,2
]}

Liu, Huisheng ^{[1
]}

Lu, Jianfeng ^{[1
]}

Qian, Kun ^{[1
,3
]}

Huang, CindyTzu-Ling ^{[1
]}

Zhong, Xiaofen ^{[1
]}

Fan, Frank ^{[4
]}

Zhang, Su-Chun ^{[1
,5
,6
]}

机构：

[1] Univ Wisconsin, Waisman Ctr, Madison, WI 53705 USA

[2] Huazhong Univ Sci & Technol, Tongji Hosp, Tongji Med Coll, Dept Rehabil Med, Wuhan 430030, Peoples R China

[3] Huazhong Univ Sci & Technol, Tongji Hosp, Tongji Med Coll, Reprod Med Ctr,Tongji Hosp, Wuhan 430030, Peoples R China

[4] Promega Corp, Madison, WI 53711 USA

[5] Univ Wisconsin, Sch Med & Publ Hlth, Dept Neurosci, Madison, WI 53705 USA

[6] Univ Wisconsin, Sch Med & Publ Hlth, Dept Neurol, Madison, WI 53705 USA

来源：

NATURE COMMUNICATIONS | 2015年 / 6卷

关键词：

DIRECTED DIFFERENTIATION; EFFICIENT GENERATION; ALS; SPECIFICATION; INHIBITOR; PRECURSORS; EXPRESSION; IPSCS;

D O I：

10.1038/ncomms7626

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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 x 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.

引用

页数：9

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