AUTHOR=Galiakberova Adelya Albertovna , Brovkina Olga Igorevna , Kondratyev Nikolay Vitalyevich , Artyuhov Alexander Sergeevich , Momotyuk Ekaterina Dmitrievna , Kulmukhametova Olga Nikolaevna , Lagunin Alexey Aleksandrovich , Shilov Boris Vladimirovich , Zadorozhny Anton Dmitrievich , Zakharov Igor Sergeevitch , Okorokova Larisa Sergeevna , Golimbet Vera Evgenievna , Dashinimaev Erdem Bairovich 

TITLE=Different iPSC-derived neural stem cells shows various spectrums of spontaneous differentiation during long term cultivation

JOURNAL=Frontiers in Molecular Neuroscience

VOLUME=Volume 16 - 2023

YEAR=2023

URL=https://www.frontiersin.org/journals/molecular-neuroscience/articles/10.3389/fnmol.2023.1037902

DOI=10.3389/fnmol.2023.1037902

ISSN=1662-5099

ABSTRACT=Culturing of human neural stem cells (NSCs) derived from induced pluripotent stem cells (iPSC) is a promising area of research, as these cells have the potential to treat a wide range of neurological, neurodegenerative and psychiatric diseases. However, the development of optimal protocols for the production and long-term culturing of NSCs remains a challenge. One of the most important aspects of this problem is to determine the stability of NSCs during long-term in vitro passaging. To address this problem, our study was aimed at investigating the spontaneous differentiation profile in different iPSC-derived human NSCs cultures during long-term cultivation using immunocytochemistry, qPCR, bulk transcriptomes and scRNA-seq. Our results indicate a significant dependence of the spectrum of differentiated cells on both the number of passages and the original iPSC lineage, suggesting that both internal (genetic and epigenetic) and external (conditions and duration of cultivation) factors influence the stability of NSCs. These results have important implications for the development of optimal NSCs culturing protocols and highlight the need to further investigate the factors influencing the stability of these cells in vitro.