High-efficiency motor neuron differentiation from human pluripotent stem cells and the function of Islet-1
| Autor: | Stephanie Tsang, Jiaxi Zhou, Jianjun Cheng, Kathleen R. Louis, Charles L. Cox, Qiuhao Qu, Dong Li, Fei Wang, Qinyu Sun, Shane R. Crandall, Xiangzhen Li, Hong Yang |
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| Rok vydání: | 2013 |
| Předmět: |
Pluripotent Stem Cells
Interneuron LIM-Homeodomain Proteins General Physics and Astronomy Biology Real-Time Polymerase Chain Reaction Regenerative medicine General Biochemistry Genetics and Molecular Biology Cell Line Mice medicine Animals Humans Induced pluripotent stem cell Progenitor Motor Neurons Multidisciplinary Drug discovery Cell Differentiation General Chemistry Anatomy Motor neuron Cell biology Electrophysiology medicine.anatomical_structure Cell culture Function (biology) Transcription Factors |
| Zdroj: | Nature communications. 5 |
| ISSN: | 2041-1723 |
| Popis: | Efficient derivation of large-scale motor neurons (MNs) from human pluripotent stem cells is central to the understanding of MN development, modelling of MN disorders in vitro and development of cell-replacement therapies. Here we develop a method for rapid (20 days) and highly efficient (~70%) differentiation of mature and functional MNs from human pluripotent stem cells by tightly modulating neural patterning temporally at a previously undefined primitive neural progenitor stage. This method also allows high-yield (>250%) MN production in chemically defined adherent cultures. Furthermore, we show that Islet-1 is essential for formation of mature and functional human MNs, but, unlike its mouse counterpart, does not regulate cell survival or suppress the V2a interneuron fate. Together, our discoveries improve the strategy for MN derivation, advance our understanding of human neural specification and MN development, and provide invaluable tools for human developmental studies, drug discovery and regenerative medicine. |
| Databáze: | OpenAIRE |
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