title: Rapid Ngn2-induction of excitatory neurons from hiPSC-derived neural progenitor cells.
abstract: Since the discovery of somatic reprogramming, human induced pluripotent stem cells (hiPSCs) have been exploited to model a variety of neurological and psychiatric disorders. Because hiPSCs represent an almost limitless source of patient-derived neurons that retain the genetic variations thought to contribute to disease etiology, they have been heralded as a patient-specific platform for high throughput drug screening. However, the utility of current protocols for generating neurons from hiPSCs remains limited by protracted differentiation timelines and heterogeneity of the neuronal phenotypes produced. Neuronal induction via the forced expression of exogenous transcription factors rapidly induces defined populations of functional neurons from fibroblasts and hiPSCs. Here, we describe an adapted protocol that accelerates maturation of functional excitatory neurons from hiPSC-derived neural progenitor cells (NPCs) via lentiviral transduction of Neurogenin 2 (using both mNgn2 and hNGN2). This methodology, relying upon a robust and scalable starting population of hiPSC NPCs, should be readily amenable to scaling for hiPSC-based high-throughput drug screening.
authors.affiliation: Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY 10029, United States; Developmental and Stem Cell Biology, The Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, United States; Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, United States.
authors.forename: Seok-Man
authors.initials: SM
authors.lastname: Ho
authors.affiliation: Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY 10029, United States; Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, United States.
authors.forename: Brigham J
authors.initials: BJ
authors.lastname: Hartley
authors.affiliation: Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY 10029, United States; Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY 10029, United States; Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, United States.
authors.forename: Julia
authors.initials: J
authors.lastname: Tcw
authors.affiliation: Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY 10029, United States; Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, United States.
authors.forename: Michael
authors.initials: M
authors.lastname: Beaumont
authors.affiliation: Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY 10029, United States.
authors.forename: Khalifa
authors.initials: K
authors.lastname: Stafford
authors.affiliation: Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY 10029, United States; Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, United States.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Slesinger
authors.affiliation: Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY 10029, United States; Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY 10029, United States; Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, United States. Electronic address: kristen.brennand@mssm.edu.
authors.forename: Kristen J
authors.initials: KJ
authors.lastname: Brennand
mesh_terms: D051792:Basic Helix-Loop-Helix Proteins / Q000502:physiology*; D018929:Cell Culture Techniques; D002478:Cells, Cultured; D065150:Cellular Reprogramming; D015870:Gene Expression; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000502:physiology*; D016086:Lentivirus; D009419:Nerve Tissue Proteins / Q000502:physiology*; D058953:Neural Stem Cells / Q000502:physiology; D015533:Transcriptional Activation
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D009419:Nerve Tissue Proteins; C491183:NEUROG2 protein, human
keywords: Directed differentiation; Modeling neuropsychiatric disease; Neuronal induction; hiPSC; iNeuron