title: Identifying division symmetry of mouse embryonic stem cells: negative impact of DNA methyltransferases on symmetric self-renewal.
abstract: Cell division is a process by which a mother cell divides into genetically identical sister cells, although sister cells often display considerable diversity. In this report, over 350 sister embryonic stem cells (ESCs) were isolated through a microdissection method, and then expression levels of 48 key genes were examined for each sister cell. Our system revealed considerable diversities between sister ESCs at both pluripotent and differentiated states, whereas the similarity between sister ESCs was significantly elevated in a 2i (MEK and GSK3b inhibitors) condition, which is believed to mimic the ground state of pluripotency. DNA methyltransferase 3a/3b were downregulated in 2i-grown ESCs, and the loss of DNA methyltransferases was sufficient to generate nearly identical sister cells. These results suggest that DNA methylation is a major cause of the diversity between sister cells at the pluripotent states, and thus demethylation per se plays an important role in promoting ESC's self-renewal.
authors: Haemato-Oncology Research Unit, Division of Molecular Pathology, Division of Cancer Biology, The Institute of Cancer Research, Sutton SM2 5NG, UK.
authors: Lukasz
authors: L
authors: Jasnos
authors: Fatma Betül
authors: FB
authors: Aksoy
authors: Hersi Mohamed
authors: HM
authors: Hersi
authors: Slawomir
authors: S
authors: Wantuch
authors: Tomoyuki
authors: T
authors: Sawado
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002455:Cell Division / Q000235:genetics* / Q000502:physiology; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000502:physiology*; D019175:DNA Methylation; D000090205:DNA Methyltransferase 3A; D053595:Embryonic Stem Cells / Q000166:cytology*; D020869:Gene Expression Profiling; D051379:Mice; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism; D012313:RNA / Q000378:metabolism
chemical_list: C000715535:Dnmt3a protein, mouse; D012313:RNA; D004248:DNA (Cytosine-5-)-Methyltransferases; D000090205:DNA Methyltransferase 3A