期刊
METHODS
卷 101, 期 -, 页码 113-124出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.ymeth.2015.11.019
关键词
hiPSC; Directed differentiation; Neuronal induction; iNeuron; Modeling neuropsychiatric disease
资金
- Brain and Behavior Young Investigator Grant
- National Institute of Health (NIH) grant [R01 MH101454]
- New York Stem Cell Foundation
- NIDA Interdisciplinary Postdoctoral Training Program in Drug Abuse Research training grant at Mount Sinai
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. (C) 2015 Elsevier Inc. All rights reserved.
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