Forkhead Transcription Factors in Stem Cell Development

描述（由申请人提供）： 细胞凋亡或程序性细胞死亡是胚胎发育的主要调节因子。造血细胞的发育需要增殖和凋亡之间的微妙平衡，这部分地由造血细胞因子调节。细胞凋亡在控制细胞数量和消除不再需要或严重受损的细胞方面起着关键作用。叉头FOXO转录因子是细胞因子缺乏的造血细胞中程序性细胞死亡的关键调节因子。这些高度保守的转录因子除了参与细胞凋亡的调节外，还参与许多基本的生物学反应。重要的是，在某些人类肿瘤和白血病的染色体重排位点也发现了FOXO转录因子。尽管由于造血细胞因子剥夺和它们在白血病中的失调而导致它们的凋亡作用，但FOXO转录因子在造血细胞正常发育期间的功能尚不清楚。这些研究旨在研究这些蛋白质的表达和功能，以及它们在使用小鼠胚胎干细胞系统的造血系统的发生和发育中的潜在参与。

DESCRIPTION (provided by applicant): Apoptosis or programmed cell death is a major regulator of embryonic development. The development of hematopoietic cells requires a delicate balance between proliferation and apoptosis that is regulated in part by hematopoietic cytokines. Apoptosis plays a critical role in controlling the number of cells and eliminating cells that are no longer needed or are seriously damaged. Forkhead FOXO transcription factors are key regulators of programmed cell death in cytokine deprived hematopoietic cells. These highly conserved transcription factors, are involved in many fundamental biological responses in addition to the regulation of apoptosis. Importantly, FOXO transcription factors have also been identified at the sites of chromosomal rearrangements in certain human tumors and leukemias. Despite their apoptotic role as a result of hematopoietic cytokine deprivation and their dysregulation in leukemia, the function of FOXO transcription factors during normal development of blood forming cells is not known. These studies are aimed at investigating the expression and the function of these proteins and their potential involvement in the onset and development of the hematopoietic system using the mouse embryonic stem cell system.