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
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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