title: Functional maturation of hPSC-derived forebrain interneurons requires an extended timeline and mimics human neural development.
abstract: Directed differentiation from human pluripotent stem cells (hPSCs) has seen significant progress in recent years. However, most differentiated populations 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 posttransplantation 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 7 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.
authors: The Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, Department of Neurology, University of California, San Francisco, San Francisco, CA 94158, USA.
authors: Cory R
authors: CR
authors: Nicholas
authors: Jiadong
authors: J
authors: Chen
authors: Yunshuo
authors: Y
authors: Tang
authors: Derek G
authors: DG
authors: Southwell
authors: Nadine
authors: N
authors: Chalmers
authors: Daniel
authors: D
authors: Vogt
authors: Christine M
authors: CM
authors: Arnold
authors: Ying-Jiun J
authors: YJ
authors: Chen
authors: Edouard G
authors: EG
authors: Stanley
authors: Andrew G
authors: AG
authors: Elefanty
authors: Yoshiki
authors: Y
authors: Sasai
authors: Arturo
authors: A
authors: Alvarez-Buylla
authors: John L R
authors: JL
authors: Rubenstein
authors: Arnold R
authors: AR
authors: Kriegstein
mesh_terms: D000200:Action Potentials; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics; D002455:Cell Division / Q000235:genetics; D059330:GABAergic Neurons / Q000166:cytology / Q000378:metabolism; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D007395:Interneurons / Q000166:cytology* / Q000378:metabolism; D008473:Median Eminence / Q000166:cytology; D051379:Mice; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism; D055495:Neurogenesis / Q000235:genetics; D009457:Neuroglia / Q000166:cytology / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D016548:Prosencephalon / Q000166:cytology*; D013569:Synapses / Q000378:metabolism; D013687:Telencephalon / Q000166:cytology; D000074482:Thyroid Nuclear Factor 1; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D015415:Biomarkers; D009687:Nuclear Proteins; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors; D049452:Green Fluorescent Proteins
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