title: Epigenetics of cell fate reprogramming and its implications for neurological disorders modelling.
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.
authors.affiliation: Faculty of Veterinary Medicine, University of Life Sciences in Lublin, Akademicka 12, 20-950 Lublin, Poland; Department of Molecular Biology, Institute of Genetics and Animal Breeding, Polish Academy of Sciences, Jastrzębiec, Postępu 36A, 05-552 Magdalenka, Poland. Electronic address: grzybek.genetics@gmail.com.
authors.forename: Maciej
authors.initials: M
authors.lastname: Grzybek
authors.affiliation: Department of Biotechnology, Faculty of Civil and Environmental Engineering, Bialystok University of Technology, Wiejska 45E, 15-351 Bialystok, Poland. Electronic address: olau.95@gmail.com.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Golonko
authors.affiliation: Department of Animal Behavior, Institute of Genetics and Animal Breeding, Polish Academy of Sciences, Jastrzębiec, Postępu 36A, 05-552 Magdalenka, Poland. Electronic address: martawalczak@yahoo.com.
authors.forename: Marta
authors.initials: M
authors.lastname: Walczak
authors.affiliation: Department of Molecular Biology, Institute of Genetics and Animal Breeding, Polish Academy of Sciences, Jastrzębiec, Postępu 36A, 05-552 Magdalenka, Poland; iPS Cell-Based Disease Modelling Group, Max Delbrück Center for Molecular Medicine (MDC) in the Helmholtz Association, Robert-Rössle-Str. 10, 13092 Berlin, Germany. Electronic address: pawel.lisowski@mdc-berlin.de.
authors.forename: Pawel
authors.initials: P
authors.lastname: Lisowski
mesh_terms: D000818:Animals; D065150:Cellular Reprogramming / Q000235:genetics* / Q000502:physiology*; D044127:Epigenesis, Genetic; D057890:Epigenomics; D006801:Humans; D009422:Nervous System Diseases / Q000235:genetics* / Q000503:physiopathology*; D039904:Pluripotent Stem Cells / Q000502:physiology
keywords: Epigenetics; Epigenomics; Genome editing; Neurological disorders; Neuronal differentiation; Stem cell reprogramming; Stem cell technologies; iPS cell based disease modelling