UTX: A novel regulator of decidualization?

项目摘要 在怀孕期间，子宫内膜间质细胞转分化为蜕膜细胞，这是一个过程 被称为蜕膜化，以支持植入的胚胎。早孕蜕膜的发育 完整的功能需要协调的细胞增殖、分化和凋亡。尽管有一个 一系列优雅的研究在孕激素受体信号方面取得了突破， 转录因子和生长因子信号在子宫蜕膜化、表观遗传学中的作用 监管机构的定义仍然不明确。蜕膜功能缺陷导致妊娠并发症 如流产、宫内发育受限、妊娠丢失等。因此，身份识别 支持蜕膜化的分子机制的研究具有根本的重要性。建立在 在子宫中使用条件基因敲除小鼠模型的新的初步发现 提案将确定赖氨酸去甲基酶，UTX，在形成完整的 了解UTX如何调节子宫内膜间质细胞分化。多管齐下 已经提出了一种结合遗传、细胞和分子工具的方法。调查结果 有望建立一种新的范式来理解表观遗传调节因子在 子宫生物学。因此，拟议研究的完成将产生重大影响， 子宫内膜功能障碍和妊娠丢失治疗中潜在的翻译含义 与蜕膜化缺陷有关。

Project Summary During pregnancy, endometrial stromal cells transdifferentiate into decidual cells, a process known as decidualization, to support the implanting embryos. The development of decidua with full functionality requires coordinated cell proliferation, differentiation, and apoptosis. Despite a series of elegant studies that have made breakthroughs in progesterone receptor signaling, transcription factors, and growth factor signaling in uterine decidualization, the role of epigenetic regulators remains poorly defined. Defective decidualization leads to pregnancy complications such as miscarriage, intrauterine growth restriction, and pregnancy loss. Therefore, identification of molecular mechanisms underpinning decidualization is of fundamental importance. Built on novel preliminary findings using conditional knockout mouse model of UTX in the uterus, this proposal will identify the function of a lysine demethylase, UTX, in the development of an integral decidua and decipher how UTX regulates endometrial stromal cell differentiation. A multipronged approach incorporating genetic, cellular, and molecular tools has been proposed. The findings are anticipated to establish a new paradigm in understanding the role of epigenetic regulators in uterine biology. Thus, completion of the proposed studies will have a substantial impact, with potential translational implications in the treatment of endometrial dysfunction and pregnancy loss associated with decidualization defects.