《生命科学》 2025, 37(4): 359-371
克隆性造血的环境驱动因素及相关机制研究进展
摘 要：
克隆性造血(clonal hematopoiesis, CH) 是指循环系统中由携带驱动突变( 从点突变到染色体畸变)的造血干细胞分化而来的血细胞比例持续增加的现象，是一系列慢性疾病和全因死亡率的独立危险因素。随着暴露组学的兴起，各类环境暴露物对人体的健康效应及其机制备受关注。大规模人群队列的基因组和暴露组数据显示，CH 流行率与人群的内外环境暴露密切相关。因此，CH 是联系环境暴露与特定疾病表型的关键纽带，也是疾病防控端口前移的潜在落脚点。阐明不同环境因素驱动CH 的特异性机制和共有性机制是有效预防CH 和相关疾病的重要前提。本文重点讨论了与CH 相关的环境驱动因素以及环境- 遗传互作对CH 的影响及分子机制，并总结各类环境因素诱发CH 的共同途径—— 炎症反应。相关综述成果将为推动环境健康研究和预防医学的变革提供理论参考。
通讯作者：郭锡汉 , Email:guo_xihan@163.com
Abstract:
Clonal hematopoiesis (CH) refers to the phenomenon of increased proportion of blood cells differentiated
from hematopoietic stem cells with driver mutations (ranging from point mutations to chromosome aberrations) in the circulatory system, and it’s an independent risk factor for a range of chronic diseases and all-cause mortality. With the rise of exposomics, the effects of exposure to various environmental factors and their mechanisms have attracted extensive attention. The genomic and exposure data from large-scale population cohorts indicate that CH is closely related to the environmental exposure of population. Therefore, CH is the key linker between environmental exposure and specific disease phenotypes, and a potential foothold to push forward the port for disease prevention and control. Elucidating the specific mechanism and co-mechanism of environmental factors affecting CH is an important prerequisite for effective prevention of CH and the related diseases. This review discusses the environmental driver factors related to CH and the influence of environment-gene interaction on CH and the mechanisms, and summarizes the common pathway underlying environment-derived CH—the inflammation. The results of this review will provide theoretical reference for promoting the reform of environmental health research and preventive medicine model.
Communication Author：GUO Xi-Han , Email:guo_xihan@163.com
