撰文丨王聪 编辑丨王多鱼 排版丨水成文 新陈代谢是生物学的一个重要组成部分，通过 RNA 的转录和翻译过程实现快速且广泛的重编程。代谢还控制着负责可逆 RNA 修饰 （例如 m 6 A） 的酶的活 性。 m 6 A 是高等真核生物中 mRNA 上最常见的内部修饰。m 6 A 具有广泛的影响，已被证明参与 RNA 稳定性、剪接和翻译的调控，而 m 6 A 的失调则与多种发育 疾病以及癌症的发展密切相关。m 6 A 修饰由 METTL3–METTL14 复合物催化，这是一种 S-腺苷甲硫氨酸 （SAM） 依赖的 RNA 甲基转移酶。FTO 作为首个 RNA 去甲基化酶的发现，则突显了 m 6 A 修饰的可逆性和动态性。 代谢在影响表观遗传学和细胞命运决定方面发挥着重要作用。然而，代谢酶和代谢物以及它们在 RNA 表观遗传学中的调控机制，目前仍不清楚。 然而，甲硫氨酸代谢是否涉及独立于 S-腺苷甲硫氨酸 （SAM） 的表观遗传机制，以及此类机制在肿瘤发生中发挥何种作用，目前仍不清楚。 在这项最新研究中，研究团队发现， 腺苷高半胱氨酸酶 （Adenosylhomocysteinase，AHCY） - 腺苷 （ADO） ...

Core Viewpoint - The study published in Cell highlights that chronic metabolic stress from high-fat diets not only leads to fatty liver but also induces profound changes in liver stem cells, which can promote tumorigenesis [1][2]. Group 1: Research Findings - Chronic stress forces liver cells to choose between survival and maintaining organ function, leading to early adaptive changes that can "pre-program" future tumor development [3][4]. - The research utilized a high-fat diet mouse model to simulate human metabolic dysfunction related to fatty liver disease, tracking changes in liver cells through multi-omics analysis [5]. - Chronic metabolic stress activates two core programs in liver cells: an upregulation program that promotes cell survival and regeneration while downregulating liver-specific functions, leading to decreased liver function [6]. Group 2: Key Mechanisms - The decline of the ketogenesis rate-limiting enzyme HMGCS2 is crucial, as its knockout in liver cells under high-fat diet stress exacerbates stress responses and significantly increases tumor incidence [8]. - The transcription factors SOX4 and RELB play a central role in promoting liver cell dedifferentiation and proliferation under stress, with high expression levels in patients with metabolic dysfunction-associated fatty liver disease (MASLD) indicating poor prognosis [10]. Group 3: Clinical Implications - The study reveals a "memory effect" of chronic stress and suggests monitoring the expression of genes like HMGCS2 and SOX4 as early risk markers for liver cancer [14]. - Targeting metabolic pathways, such as ketogenesis, or transcription factors like SOX4 may block precancerous states, providing potential intervention strategies [15]. - Overall, the adaptation of the liver to chronic metabolic stress enhances short-term cell survival but sacrifices long-term liver function, emphasizing the importance of healthy diets and metabolic stress control in preventing liver cancer [17].

Core Insights - Congenital heart disease is the most common type of birth defect in newborns, and recent research by Chinese scientists has identified an organ primordium determination zone that provides a crucial theoretical basis for the prevention and treatment of congenital heart disease and other birth defects [1][3] - The study, published in the international academic journal "Cell," utilized single-cell spatial omics analysis to capture the dynamic process of organ formation in mouse embryos, focusing on the early stages of development [1][3] Research Findings - The research team discovered a unique signaling "depression" known as the organ primordium determination zone (PDZ) at 7.75 days of mouse embryonic development, characterized by low signal activity and the expression of various receptor signaling genes [3] - The PDZ area is surrounded by high concentrations of inhibitory and activating signaling molecules, creating a microenvironment conducive to the coordinated development of the heart and foregut [3] - This study provides a new methodology for understanding organ regeneration and tumorigenesis, offering precise scientific evidence for the prevention and treatment of congenital heart disease and related conditions [3]