Generation of functional posterior spinal motor neurons from hPSCs-derived human spinal cord neural progenitor cells

被引:6
作者
Xu, He Jax [1 ,2 ]
Yao, Yao [1 ,2 ]
Yao, Fenyong [3 ]
Chen, Jiehui [1 ,2 ]
Li, Meishi [2 ,4 ]
Yang, Xianfa [1 ,2 ,5 ]
Li, Sheng [1 ,6 ]
Lu, Fangru [4 ]
Hu, Ping [1 ,2 ,5 ,6 ,7 ]
He, Shuijin [3 ]
Peng, Guangdun [2 ,4 ,7 ,8 ]
Jing, Naihe [1 ,2 ,5 ,7 ]
机构
[1] Chinese Acad Sci, Shanghai Inst Biochem & Cell Biol, CAS Ctr Excellence Mol Cell Sci, State Key Lab Cell Biol, Shanghai 200031, Peoples R China
[2] Univ Chinese Acad Sci, Beijing, Peoples R China
[3] ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China
[4] Chinese Acad Sci, Ctr Cell Lineage & Dev, CAS Key Lab Regenerat Biol, Guangdong Prov Key Lab Stem Cell & Regenerat Med,G, Guangzhou 510530, Peoples R China
[5] Bioland Lab, Guangzhou Lab, Guangzhou 510005, Peoples R China
[6] Shanghai Jiao Tong Univ, Sch Med, Xinhua Hosp, Shanghai 20023, Peoples R China
[7] Chinese Acad Sci, Inst Stem Cell & Regenerat, Beijing 100101, Peoples R China
[8] Bioland Lab, Ctr Cell Lineage & Atlas, Guangzhou 510005, Peoples R China
关键词
Motor neuron; Motor neuron differentiation; Neuromesodermal progenitors; Neuromuscular junction; PLURIPOTENT STEM-CELLS; CENTRAL-NERVOUS-SYSTEM; DIRECTED DIFFERENTIATION; HUMAN FIBROBLASTS; POOL IDENTITY; MOUSE; SPECIFICATION; MOTONEURONS; INDUCTION; MUSCLE;
D O I
10.1186/s13619-023-00159-6
中图分类号
Q813 [细胞工程];
学科分类号
摘要
Spinal motor neurons deficiency results in a series of devastating disorders such as amyotrophic lateral sclerosis (ALS), spinal muscular atrophy (SMA) and spinal cord injury (SCI). These disorders are currently incurable, while human pluripotent stem cells (hPSCs)-derived spinal motor neurons are promising but suffered from inappropriate regional identity and functional immaturity for the study and treatment of posterior spinal cord related injuries. In this study, we have established human spinal cord neural progenitor cells (hSCNPCs) via hPSCs differentiated neuromesodermal progenitors (NMPs) and demonstrated the hSCNPCs can be continuously expanded up to 40 passages. hSCNPCs can be rapidly differentiated into posterior spinal motor neurons with high efficiency. The functional maturity has been examined in detail. Moreover, a co-culture scheme which is compatible for both neural and muscular differentiation is developed to mimic the neuromuscular junction (NMJ) formation in vitro. Together, these studies highlight the potential avenues for generating clinically relevant spinal motor neurons and modeling neuromuscular diseases through our defined hSCNPCs.
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页数:21
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