Direct Induction and Functional Maturation of Forebrain GABAergic Neurons from Human Pluripotent Stem Cells

Autor: Levana L. Sani, Hoang-Dai Tran, Shawn Tan, Danlei Wang, Kea Joo Lee, Paul Jong Kim, Qiang Yuan, Huck-Hui Ng, Hyunsoo Shawn Je, Yi-Chun Yen, Yixin Xiao, Alfred Xuyang Sun, Bing Lim, Yong Seng Chiew, Audrey Tze Ting Khoo
Rok vydání: 2015
Předmět:
0301 basic medicine
Patch-Clamp Techniques
Thyroid Nuclear Factor 1
Gene Expression
Mice
SCID
Synaptic Transmission
Synapse
GABA
Mice
0302 clinical medicine
Neural Stem Cells
synapse
Mice
Inbred NOD
Basic Helix-Loop-Helix Transcription Factors
direct conversion
human pluripotent stem cells
GABAergic Neurons
Induced pluripotent stem cell
lcsh:QH301-705.5
gamma-Aminobutyric Acid
Cerebral Cortex
Nuclear Proteins
Cell Differentiation
Anatomy
Neural stem cell
medicine.anatomical_structure
GABAergic
Neuroglia
Pluripotent Stem Cells
Interneuron
LIM-Homeodomain Proteins
Primary Cell Culture
Nerve Tissue Proteins
interneuron
Biology
General Biochemistry
Genetics and Molecular Biology
Cell Line
03 medical and health sciences
Glutamatergic
Prosencephalon
Interneurons
Biological neural network
medicine
Animals
Humans
Homeodomain Proteins
Coculture Techniques
Transplantation
030104 developmental biology
nervous system
lcsh:Biology (General)
Synapses
Neuroscience
030217 neurology & neurosurgery
Biomarkers
Transcription Factors
Zdroj: Cell Reports, Vol 16, Iss 7, Pp 1942-1953 (2016)
ISSN: 2211-1247
Popis: SummaryGamma-aminobutyric acid (GABA)-releasing interneurons play an important modulatory role in the cortex and have been implicated in multiple neurological disorders. Patient-derived interneurons could provide a foundation for studying the pathogenesis of these diseases as well as for identifying potential therapeutic targets. Here, we identified a set of genetic factors that could robustly induce human pluripotent stem cells (hPSCs) into GABAergic neurons (iGNs) with high efficiency. We demonstrated that the human iGNs express neurochemical markers and exhibit mature electrophysiological properties within 6–8 weeks. Furthermore, in vitro, iGNs could form functional synapses with other iGNs or with human-induced glutamatergic neurons (iENs). Upon transplantation into immunodeficient mice, human iGNs underwent synaptic maturation and integration into host neural circuits. Taken together, our rapid and highly efficient single-step protocol to generate iGNs may be useful to both mechanistic and translational studies of human interneurons.
Databáze: OpenAIRE
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