Department of Systems Biology, Harvard Medical School, Boston, MA 02115.
Department of Systems Biology, Harvard Medical School, Boston, MA 02115
Proc Natl Acad Sci U S A. 2014 Jul 1;111(26):9503-8. doi: 10.1073/pnas.1408638111. Epub 2014 Jun 16.
Attainment of the differentiated state during the final stages of somatic cell differentiation is closely tied to cell cycle progression. Much less is known about the role of the cell cycle at very early stages of embryonic development. Here, we show that molecular pathways involving the cell cycle can be engineered to strongly affect embryonic stem cell differentiation at early stages in vitro. Strategies based on perturbing these pathways can shorten the rate and simplify the lineage path of ES differentiation. These results make it likely that pathways involving cell proliferation intersect at various points with pathways that regulate cell lineages in embryos and demonstrate that this knowledge can be used profitably to guide the path and effectiveness of cell differentiation of pluripotent cells.
在体细胞分化的最后阶段获得分化状态与细胞周期进程密切相关。在胚胎发育的早期阶段,细胞周期的作用知之甚少。在这里,我们表明,可以设计涉及细胞周期的分子途径,以强烈影响体外早期胚胎干细胞的分化。基于这些途径的干扰策略可以缩短 ES 分化的速率并简化谱系途径。这些结果表明,涉及细胞增殖的途径与调节胚胎细胞谱系的途径在多个点相交,并证明可以利用这些知识来指导多能细胞的细胞分化路径和有效性。