Induction of human somatostatin and parvalbumin neurons by expressing a single transcription factor LIM homeobox 6

• DOI: 10.7554/elife.37382
• Publication Date: 2018-09-25T12:00:15Z
• Authors: 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
• Keywords: Homeobox A1; Ganglionic eminence

Human GABAergic interneurons (GIN) are implicated in normal brain function and numerous mental disorders. However, the generation of functional human GIN subtypes from pluripotent stem cells (hPSCs) has not been established. By expressing LHX6, a transcriptional factor that is critical for development, we induced hPSCs to form GINs, including somatostatin (SST, 29%) parvalbumin (PV, 21%) neurons. Our RNAseq results also confirmed alteration identity with overexpression LHX6. Five months after transplantation into mouse brain, GABA precursors generated increased population SST PV neurons by overexpressing Importantly, grafted GINs exhibited electrophysiological properties even fast-spiking-like action potentials. Thus, expression single transcription LHX6 under our differentiation condition sufficient robustly induce subtypes.