Overcoming the hurdles for a reproducible generation of human functionally mature reprogrammed neurons

Experimental Biology and Medicine
Vania BroccoliLatefa Yekhlef

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.

References

Dec 4, 2001·Nature Biotechnology·B E ReubinoffT Ben-Hur
Dec 17, 2005·Stem Cells·Anna M KrichevskyKenneth S Kosik
Mar 23, 2007·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·M Austin JohnsonSu-Chun Zhang
Aug 19, 2007·Proceedings of the National Academy of Sciences of the United States of America·Hao WuYi E Sun
Dec 23, 2008·Nature·Allison D EbertClive N Svendsen
Mar 17, 2009·Nature Neuroscience·Li-Chun ChengFiona Doetsch
Jan 29, 2010·Nature·Thomas VierbuchenMarius Wernig
Feb 9, 2010·Nature Methods·Fangjun JiaJoseph C Wu
Feb 18, 2010·Proceedings of the National Academy of Sciences of the United States of America·Bao-Yang HuSu-Chun Zhang
May 28, 2011·Nature·Zhiping P PangMarius Wernig
Jun 8, 2011·Proceedings of the National Academy of Sciences of the United States of America·Ulrich PfistererMalin Parmar
Jul 15, 2011·Nature·Andrew S YooGerald R Crabtree
Aug 20, 2011·Cell Stem Cell·Esther Y SonKevin Eggan
Nov 23, 2011·Cell Research·Xinjian LiuChuan-Yuan Li
Jan 27, 2012·Nature·Mason A IsraelLawrence S B Goldstein
Apr 10, 2012·Nature Methods·Julia LadewigOliver Brüstle
May 9, 2012·Cell Stem Cell·Shila MekhoubadKevin Eggan
Jan 11, 2013·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Mackenzie W AmorosoHynek Wichterle
Feb 23, 2013·Nature Protocols·Pankaj K Mandal, Derrick J Rossi
Mar 27, 2013·Proceedings of the National Academy of Sciences of the United States of America·Olof TorperMalin Parmar
Aug 21, 2013·Stem Cells and Development·Pu WangJianhong Zhu
Mar 1, 2014·Nature Protocols·Uri Ben-David, Nissim Benvenisty
Mar 4, 2014·PloS One·Elizabeth M HartfieldRichard Wade-Martins
Sep 26, 2014·Stem Cell Reports·Soham ChandaMarius Wernig

❮ Previous
Next ❯

Citations

Dec 15, 2015·Molecular and Cellular Neurosciences·Alison E MungenastLi-Huei Tsai
Apr 17, 2018·Royal Society Open Science·Giovanna M D'AbacoEfstratios Skafidas
Aug 16, 2016·EMBO Molecular Medicine·Daniel I OrellanaSonia Levi
Jan 12, 2021·Molecular Therapy : the Journal of the American Society of Gene Therapy·Gabriella MacDougallOrnit Chiba-Falek

❮ Previous
Next ❯

Related Concepts

Related Feeds

Adult Stem Cells

Adult stem cells reside in unique niches that provide vital cues for their survival, self-renewal, and differentiation. They hold great promise for use in tissue repair and regeneration as a novel therapeutic strategies. Here is the latest research.

Amyloid Lateral Sclerosis

Amyotrophic Lateral Sclerosis (ALS) is a progressive nervous system disease associated with the death of neurons that control voluntary muscles. Discover the latest research on ALS here.

Basal Ganglia

Basal Ganglia are a group of subcortical nuclei in the brain associated with control of voluntary motor movements, procedural and habit learning, emotion, and cognition. Here is the latest research.