title: Maintenance of pluripotency in mouse ES cells without Trp53.
abstract: Tumor suppressor Trp53 works as a guardian of the genome in somatic cells. In mouse embryonic stem (ES) cells, it was reported that Trp53 represses pluripotency-associated transcription factor Nanog to induce differentiation. However, since Trp53-null mice develop to term, Trp53 is dispensable for both the maintenance and differentiation of the pluripotent stem cell population in vivo, suggesting the differential functions of Trp53 in ES cells and embryos. To reveal the basis of this discrepancy, here we established a new line of Trp53-null ES cells by sequential gene targeting and evaluated their ability to differentiate in vitro and in vivo. We found that Trp53-null ES cells had defects in differentiation in vitro as reported previously, whereas they were able to contribute to normal development in chimeric embryos. These data indicated that the requirement of Trp53 for maintaining and executing the ES pluripotency is not absolute.
authors.affiliation: Laboratory for Pluripotent Stem Cell Studies, RIKEN Center for Developmental Biology (CDB), 2-2-3 Minatojima-minamimachi, Chuo-ku, Kobe 6500047, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Shigeta
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ohtsuka
authors.forename: Satomi
authors.initials: S
authors.lastname: Nishikawa-Torikai
authors.forename: Mariko
authors.initials: M
authors.lastname: Yamane
authors.forename: Setsuko
authors.initials: S
authors.lastname: Fujii
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Murakami
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Niwa
mesh_terms: D000782:Aneuploidy; D000818:Animals; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D002460:Cell Line; D002678:Chimera; D047108:Embryonic Development / Q000235:genetics; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D015870:Gene Expression; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D055786:Gene Knockout Techniques; D023061:Gene Order; D018390:Gene Targeting; D005838:Genotype; D007621:Karyotyping; D053605:Leukemia Inhibitory Factor / Q000494:pharmacology; D051379:Mice; D021381:Protein Transport; D016159:Tumor Suppressor Protein p53 / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism
chemical_list: D053605:Leukemia Inhibitory Factor; D016159:Tumor Suppressor Protein p53