title: Overcoming the hurdles for a reproducible generation of human functionally mature reprogrammed neurons.
abstract: The advent of cell reprogramming technologies has widely disclosed the possibility to have direct access to human neurons for experimental and biomedical applications. Human pluripotent stem cells can be instructed in vitro to generate specific neuronal cell types as well as different glial cells. Moreover, new approaches of direct neuronal cell reprogramming can strongly accelerate the generation of different neuronal lineages. However, genetic heterogeneity, reprogramming fidelity, and time in culture of the starting cells can still significantly bias their differentiation efficiency and quality of the neuronal progenies. In addition, reprogrammed human neurons exhibit a very slow pace in gaining a full spectrum of functional properties including physiological levels of membrane excitability, sustained and prolonged action potential firing, mature synaptic currents and synaptic plasticity. This delay poses serious limitations for their significance as biological experimental model and screening platform. We will discuss new approaches of neuronal cell differentiation and reprogramming as well as methods to accelerate the maturation and functional activity of the converted human neurons.
authors: Stem cells and Neurogenesis, San Raffaele Scientific Institute, Milan 20132, Italy broccoli.vania@hsr.it.
authors: Vania
authors: V
authors: Broccoli
authors: Stem cells and Neurogenesis, San Raffaele Scientific Institute, Milan 20132, Italy.
authors: Alicia
authors: A
authors: Rubio
authors: Neuroimmunology Unit, Division of Neuroscience, San Raffaele Scientific Institute, Milan 20132, Italy.
authors: Stefano
authors: S
authors: Taverna
authors: Neuroimmunology Unit, Division of Neuroscience, San Raffaele Scientific Institute, Milan 20132, Italy.
authors: Latefa
authors: L
authors: Yekhlef
mesh_terms: D002454:Cell Differentiation; D065150:Cellular Reprogramming; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism*; D009473:Neuronal Plasticity; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D009435:Synaptic Transmission
keywords: Neurons; disease modeling; embryonic stem cells; induced pluripotent stem cells; neuronal activity; synapses