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| Status |
Public on May 03, 2013 |
| Title |
MicroArray Gene Expression Profiling of NKX2.1-GFP+ MGE-like Interneuron Precursors Derived from Human Embryonic Stem Cells |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Human embryonic stem cells with a GFP reporter knock-in into the NKX2.1 locus were differentiated and purified by FACS sorting for global gene expression analysis.
Directed differentiation from human pluripotent stem cells (hPSCs) has seen significant progress in recent years. Most differentiated populations, however, exhibit immature properties of an early embryonic stage, raising concerns about their ability to model and treat disease. Here, we report the directed differentiation of hPSCs into medial ganglionic eminence (MGE)-like progenitors and their maturation into forebrain type interneurons. We find that early stage progenitors progress via a radial glial-like stem cell enriched in the human fetal brain. Both in vitro and post-transplantation into the rodent cortex, the MGE-like cells develop into GABAergic interneuron subtypes with mature physiological properties along a prolonged intrinsic timeline of up to seven months, mimicking endogenous human neural development. MGE-derived cortical interneuron deficiencies are implicated in a broad range of neurodevelopmental and degenerative disorders, highlighting the importance of these results for modeling human neural development and disease.
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| Overall design |
Human embryonic stem cells with a GFP reporter knock-in into the NKX2.1 locus were differentiated for 20, 35, and 55 days in vitro and GFP+ cells were purified by FACS sorting. Total RNA was prepared from each timepoint and compared to undifferentiated human embryonic stem cells. hESC = one sample and three technical replicates. D20 = three independent samples. D35 = one sample and two technical replicates. D55 = one sample and one technical replicate.
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| Contributor(s) |
Nicholas C, Chen J, Kriegstein A, Alvarez-Buylla A, Rubenstein J |
| Citation(s) |
23642366 |
| Submission date |
Apr 01, 2013 |
| Last update date |
Aug 13, 2018 |
| Contact name |
Cory R Nicholas |
| Organization name |
UCSF
|
| Department |
Neurology
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| Street address |
35 Medical center way
|
| City |
San Francisco |
| State/province |
CA |
| ZIP/Postal code |
94143 |
| Country |
USA |
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| Platforms (1) |
| GPL10558 |
Illumina HumanHT-12 V4.0 expression beadchip |
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| Samples (10)
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| Relations |
| BioProject |
PRJNA195566 |
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