Abstract 3876: Cell cycle checkpoint in vivo in developing mouse embryo liver cells

Abstract

Abstract Embryonic stem (ES) cells have a distinct cell cycle distribution and cyclins/CDKs expression. ES cells are characterized by a short G1 phase and a high proportion of cell in S and G2 phase, maintain consistent level of cyclins expression seems not to be phase dependent. However, most cell cycle studies are on mouse or human ES cell line, whether that it is really reflective in vivo is not well defined. By extracting fresh liver cells from mouse embryo, we have investigated cell cycle distribution, correspondent cyclins and CDK expression in vivo in mouse embryo from embryonic days 10.5(E10.5, liver start to develop at E9.5) to post-natal 21 days(P21). We found that most of the cells (62%) were in S and G2 phase, 38% of cells in G1 at E11.5. Upon embryo development, the proportion of cells in G1 increased, although there were still large proportion of cells in S and G2 phase (55%) at P0. The short G1 phase in early embryonic day suggests that cell phase distribution may be related with embryo cells’ pluripotency in vivo. Distinct high levels of cyclin D1, E1, A, B1 and CDK1(cdc2) expressed at E10.5, which seemed to be pluripotency related but not cell phase dependent. The cyclins and CDK level started to drop from E11.5 to post-natal (P0) suggesting that cyclins/CDKs expression reduced and became regulated with differentiation. In ES cell line, where G1 population increased with differentiation, G1 DNA-damage checkpoint was still absent. However, in response to ionizing irradiation, P0 mouse liver cells showed a short G2 population increase followed by G1 cell phase arrest indicating that at P0 or even earlier stage, G1 DNA-damage checkpoint had been established in vivo. Thus, cell cycle and cell cycle checkpoint in vivo in mouse embryo liver cells displayed both similar and differential pattern compared to that in mES cell line in vitro. Underlying mechanism such as DNA-damage checkpoint patterns and its regulation will be further discussed. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3876.