Induction of human somatostatin and parvalbumin neurons by expressing a single transcription factor LIM homeobox 6
Autor: | Lixiang Ma, Kai-Heng Fang, Yuanyuan Wang, Hai-Qin Huo, Fang Yuan, Yan Liu, Mingyan Lin, Xin Chen, Min Xu, Shuijin He, Yuejun Chen, Shi-Bo Xu |
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Jazyk: | angličtina |
Rok vydání: | 2018 |
Předmět: |
0301 basic medicine
Mouse Action Potentials SST neuron Mice SCID PV neuron Biology (General) Induced pluripotent stem cell gamma-Aminobutyric Acid Neurons education.field_of_study biology General Neuroscience Cell Differentiation General Medicine Cell biology Parvalbumins GABAergic Medicine Somatostatin Research Article Human Pluripotent Stem Cells QH301-705.5 Science Population LIM-Homeodomain Proteins Nerve Tissue Proteins General Biochemistry Genetics and Molecular Biology Cell Line 03 medical and health sciences Directed differentiation Prosencephalon Interneurons parasitic diseases Animals Humans education HiPSCs Transcription factor Body Patterning General Immunology and Microbiology Gene Expression Profiling direct differentiation GINS Transplantation 030104 developmental biology Animals Newborn biology.protein Parvalbumin Developmental Biology Transcription Factors |
Zdroj: | eLife, Vol 7 (2018) eLife |
Popis: | 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. |
Databáze: | OpenAIRE |
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