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Epigenetics of cell fate reprogramming and its implications for neurological disorders modelling

Item Type:Review
Title:Epigenetics of cell fate reprogramming and its implications for neurological disorders modelling
Creators Name:Grzybek, M. and Golonko, A. and Walczak, M. and Lisowski, P.
Abstract:The reprogramming of human induced pluripotent stem cells (hiPSCs) proceeds in a stepwise manner with reprogramming factors binding and epigenetic composition changes during transition to maintain the epigenetic landscape, important for pluripotency. There arises a question as to whether the aberrant epigenetic state after reprogramming leads to epigenetic defects in induced stem cells causing unpredictable long term effects in differentiated cells. In this review, we present a comprehensive view of epigenetic alterations accompanying reprogramming, cell maintenance and differentiation as factors that influence applications of hiPSCs in stem cell based technologies. We conclude that sample heterogeneity masks DNA methylation signatures in subpopulations of cells and thus believe that beside a genetic evaluation, extensive epigenomic screening should become a standard procedure to ensure hiPSCs state before they are used for genome editing and differentiation into neurons of interest. In particular, we suggest that exploitation of the single-cell composition of the epigenome will provide important insights into heterogeneity within hiPSCs subpopulations to fast forward development of reliable hiPSC-based analytical platforms in neurological disorders modelling and before completed hiPSC technology will be implemented in clinical approaches.
Keywords:Epigenetics, Epigenomics, Stem Cell Reprogramming, Neuronal Differentiation, Neurological Disorders, Genome Editing, Stem Cell Technologies, iPS Cell Based Disease Modelling, Animals
Source:Neurobiology of Disease
ISSN:0969-9961
Publisher:Elsevier (The Netherlands)
Volume:99
Page Range:84-120
Date:March 2017
Official Publication:https://doi.org/10.1016/j.nbd.2016.11.007
PubMed:View item in PubMed

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