西班牙巴塞罗那科技学院Nicholas Stroustrup团队利用种群异步性系统绘制衰老过程中的生物体尺度基因调控网络图。相关论文发表在2024年6月21日出版的《细胞》杂志上。
研究人员介绍了Asynch-seq，这是一种利用同源群体中基因表达异质性来研究寿命变异产生过程的方法。通过收集数千个单个个体的转录组，研究人员捕捉到了秀丽隐杆线虫的“泛转录组”——一个高度解析的非遗传变异图谱。
研究人员利用这个图谱指导了大规模扰动筛选，并发现生殖细胞和体细胞之间总mRNA含量的脱钩是衰老过程中生理异质性的最大来源，这是由多效应基因驱动的，这些基因的敲除大大减少了寿命差异。该工作证明了如何通过系统地绘制生理异质性图谱来减少衰老过程中的个体间差异。
研究人员表示，在衰老过程中，生理网络功能衰退的速度因人而异，从而导致寿命的广泛分布。虽然70%的人类寿命差异仍无法用遗传因素来解释，但人们对衰老过程中生理异质性的内在来源知之甚少。要了解复杂的生理网络是如何产生寿命差异的，人们需要新的方法。
附：英文原文
Title: Systematic mapping of organism-scale gene-regulatory networks in aging using population asynchrony
Author: Matthias Eder, Olivier M.F. Martin, Natasha Oswal, Lucia Sedlackova, Cátia Moutinho, Andrea Del Carmen-Fabregat, Simon Menendez Bravo, Arnau Sebé-Pedrós, Holger Heyn, Nicholas Stroustrup
Issue&Volume: 2024-06-21
Abstract: In aging, physiologic networks decline in function at rates that differ between individuals, producing a wide distribution of lifespan. Though 70% of human lifespan variance remains unexplained by heritable factors, little is known about the intrinsic sources of physiologic heterogeneity in aging. To understand how complex physiologic networks generate lifespan variation, new methods are needed.
Here, we present Asynch-seq, an approach that uses gene-expression heterogeneity within isogenic populations to study the processes generating lifespan variation. By collecting thousands of single-individual transcriptomes, we capture the Caenorhabditis elegans “pan-transcriptome”—a highly resolved atlas of non-genetic variation. We use our atlas to guide a large-scale perturbation screen that identifies the decoupling of total mRNA content between germline and soma as the largest source of physiologic heterogeneity in aging, driven by pleiotropic genes whose knockdown dramatically reduces lifespan variance. Our work demonstrates how systematic mapping of physiologic heterogeneity can be applied to reduce inter-individual disparities in aging.
DOI: 10.1016/j.cell.2024.05.050
Source: https://www.cell.com/cell/abstract/S0092-8674(24)00594-4