Journal article

In Vitro Differentiated Human Stem Cell-Derived Neurons Reproduce Synaptic Synchronicity Arising during Neurodevelopment

Filip Rosa, Ashutosh Dhingra, Betuel Uysal, G Dulini C Mendis, Heidi Loeffler, Gina Elsen, Stephan Mueller, Niklas Schwarz, Melissa Castillo-Lizardo, Claire Cuddy, Felicitas Becker, Peter Heutink, Christopher A Reid, Steven Petrou, Holger Lerche, Snezana Maljevic



Neurons differentiated from induced pluripotent stem cells (iPSCs) typically show regular spiking and synaptic activity but lack more complex network activity critical for brain development, such as periodic depolarizations including simultaneous involvement of glutamatergic and GABAergic neurotransmission. We generated human iPSC-derived neurons exhibiting spontaneous oscillatory activity after cultivation of up to 6 months, which resembles early oscillations observed in rodent neurons. This behavior was found in neurons generated using a more "native" embryoid body protocol, in contrast to a "fast" protocol based on NGN2 overexpression. A comparison with published data indicates that EB-de..

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Awarded by Federal Ministry of Education and Research (BMBF)

Awarded by DAAD program

Awarded by Endeavor Research Fellowship Program

Awarded by Pate/Fortune program of the Medical Faculty of the University of Tubingen

Funding Acknowledgements

We thank Drs. Ulrike Hedrich-Klimosch and Henner Koch for their excellent technical help regarding electrophysiological recordings, and Stephan Liebau and the members of his team for their highly appreciated assistance with cultures of keratinocytes. Drs. Olga Garaschuk, Andreas Hermann, Simone Mayer, Ulrike Hedrich-Klimosch, Henner Koch, and Thomas Wuttke are thanked for their helpful comments and discussion of the manuscript. This work was supported by the Federal Ministry of Education and Research (BMBF, grants 01GM1105A and 01GM1907A in the frame of the networks for rare diseases IonNeurONet and TreatION). F.R. was supported by the DAAD program (91529082) and Endeavor Research Fellowship Program (6093_2017). N.S. was in part supported by the Pate/Fortune program of the Medical Faculty of the University of Tubingen (2381-0-0). The authors declare no competing interests.