Promoting functional maturation of induced human adult neurons

Autor: Birtele Marcella, Sharma Yogita, Drouin-Ouellet Janelle, Brattas Per, Shong, Lau, Rylander-Ottosson Daniella, Parmar Malin
Rok vydání: 2018
Zdroj: NECTAR
DOI: 10.5281/zenodo.2538583
Popis: Induced neurons (iNs) are somatic cells that are directly convertedto change their fate into neurons without passing through a pluripotent state. This shortensthe process of neuronal generation compared to the use ofhuman pluripotent stem cells, and the cells maintains age-properties of the donor.Neuronal conversion of human adult cells into subtype specific and functional neurons is of value both for disease modelling and patient-specific cell therapy treatments. Our group recently published a study showing how the suppression of the REST complex shREST) is a key factor in the generation of mature neurons from human adult cells [1].The neural conversion via shREST was found to be in part, but not fully, mediated via microRNA upregulation upon inhibition of shREST. In this study, we establish conditions for long term in vitro maturation of iNs and seek to investigate the role of shREST and its relation to miR9/9*-miR124 expression in the context of iN maturation using global gene expression analysis combined with unbiased and quantitative morphological assessment and patch clamp electrophysiology. We find that boosting expression of miR-124 and miR-9 combined with the shREST contributes to the functional maturation of the iNs, as assessed with electrophysiology after several months in culture.
Databáze: OpenAIRE