UTX: A novel regulator of decidualization?

UTX：蜕膜化的新型调节剂？

• 批准号: 10390537
• 负责人: Qinglei Li
• 金额: $ 7.3万
• 依托单位: TEXAS A&M UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-02-11 至 2024-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10390537
• 关键词: Apoptosis; Binding; Biology; CRISPR/Cas technology; Cell Differentiation process; Cell Proliferation; ChIP-seq; Data; Data Set; Decidua; Decidual Cell; Decidual Cell Reactions; Defect; Development; Embryo; Endometrial; Endometrial Stromal Cell; Enhancers; Enzymes; Epigenetic Process; Fetal Growth Retardation; Functional disorder; Funding Mechanisms; Genes; Genetic; Goals; Growth Factor; Human; Implant; Knock-in Mouse; Knockout Mice; Lysine; Mediating; Mission; Molecular; Mus; National Institute of Child Health and Human Development; Pathway interactions; Pregnancy; Pregnancy Complications; Pregnancy loss; Process; Progesterone Receptors; Publishing; Receptor Signaling; Regulator Genes; Regulatory Element; Reproductive Health; Role; Series; Signal Transduction; Spontaneous abortion; Testing; Uterus; Woman; conditional knockout; early pregnancy; early pregnancy loss; epigenomics; experimental study; fetal; genome-wide; histone modification; in vitro Model; in vivo; innovation; insight; mouse model; natural Blastocyst Implantation; novel; steroid hormone; tool; transcription factor; transcriptomics; translational potential

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.

项目摘要 妊娠期间，子宫内膜间质细胞转分化为蜕膜细胞， 即蜕膜化，以支持植入的胚胎。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 一系列优雅的研究在孕酮受体信号传导方面取得了突破， 转录因子和生长因子信号在子宫蜕膜化中的作用， 监管机构的定义仍然不明确。蜕膜化缺陷导致妊娠并发症 例如流产、宫内生长受限和流产。因此，识别 对蜕膜化的分子机制的研究是至关重要的。建立在 使用子宫中UTX的条件性敲除小鼠模型的新的初步发现， 一项提案将确定赖氨酸脱甲基酶UTX的功能，在发展一个完整的 蜕膜和破译UTX如何调节子宫内膜间质细胞分化。多管齐下的 已经提出了结合遗传、细胞和分子工具的方法。这些发现 预计将建立一个新的范式，了解表观遗传调节因子的作用， 子宫生物学因此，完成拟议的研究将产生重大影响， 在治疗子宫内膜功能障碍和妊娠丢失中的潜在翻译意义 与蜕膜化缺陷有关。