Induction of human somatostatin and parvalbumin neurons by expressing a single transcription factor LIM homeobox 6
Fang Yuan,
Xin Chen,
Kai-Heng Fang,
Yuanyuan Wang,
Mingyan Lin,
Shi-Bo Xu,
Hai-Qin Huo,
Min Xu,
Lixiang Ma,
Yuejun Chen,
Shuijin He,
Yan Liu
Affiliations
Fang Yuan
Institute for Stem Cell and Neural Regeneration, School of Pharmacy, Nanjing Medical University, Nanjing, China; State Key Laboratory of Reproductive Medicine, Nanjing Medical Unveristy, Nanjing, China
Xin Chen
School of Life Science and Technology, ShanghaiTech University, Shanghai, China
Kai-Heng Fang
Institute for Stem Cell and Neural Regeneration, School of Pharmacy, Nanjing Medical University, Nanjing, China
Yuanyuan Wang
Department of Neuroscience, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, China
Mingyan Lin
Department of Neuroscience, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, China
Shi-Bo Xu
Institute for Stem Cell and Neural Regeneration, School of Pharmacy, Nanjing Medical University, Nanjing, China
Hai-Qin Huo
Institute for Stem Cell and Neural Regeneration, School of Pharmacy, Nanjing Medical University, Nanjing, China
Min Xu
Institute for Stem Cell and Neural Regeneration, School of Pharmacy, Nanjing Medical University, Nanjing, China
Lixiang Ma
Department of Human Anatomy and Histology, Institute of Stem Cells and Regenerative Medicine, Fudan University Shanghai Medical School, Shanghai, China
Yuejun Chen
Institute of Neuroscience, Chinese Academy of Sciences, Beijing, China
Shuijin He
School of Life Science and Technology, ShanghaiTech University, Shanghai, China
Institute for Stem Cell and Neural Regeneration, School of Pharmacy, Nanjing Medical University, Nanjing, China; State Key Laboratory of Reproductive Medicine, Nanjing Medical Unveristy, Nanjing, China; Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing, China
Human GABAergic interneurons (GIN) are implicated in normal brain function and in numerous mental disorders. However, the generation of functional human GIN subtypes from human pluripotent stem cells (hPSCs) has not been established. By expressing LHX6, a transcriptional factor that is critical for GIN development, we induced hPSCs to form GINs, including somatostatin (SST, 29%) and parvalbumin (PV, 21%) neurons. Our RNAseq results also confirmed the alteration of GIN identity with the overexpression of LHX6. Five months after transplantation into the mouse brain, the human GABA precursors generated increased population of SST and PV neurons by overexpressing LHX6. Importantly, the grafted human GINs exhibited functional electrophysiological properties and even fast-spiking-like action potentials. Thus, expression of the single transcription factor LHX6 under our GIN differentiation condition is sufficient to robustly induce human PV and SST subtypes.
