The impact of dietary restriction on transcriptional profiles of hematopoietic stem cells in aged female mice.

IF 4.4 4区 医学 Q1 GERIATRICS & GERONTOLOGY
Chenghui Yu, Xingxing Qiu, Si Tao, Yuanyuan Wu, Siyao He, Qiao Wang, Duozhuang Tang, Yiting Wang
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Abstract

This study investigates the impact of dietary restriction (DR) on gene expression in hematopoietic stem cells (HSCs) derived from aged mice. RNA sequencing (RNA-seq) data were obtained from sorted HSCs, followed by weighted gene co-expression network analysis (WGCNA) to identify differentially expressed genes (DEGs) and key transcriptional modules. Principal component analysis (PCA) and heatmaps revealed significant differences between the groups, highlighting a predominant upregulation of gene expression during aging and a more suppressive gene expression profile under DR. Functional enrichment analysis indicated that the aging process in HSCs is characterized by enhanced expression of genes associated with inflammatory responses and DNA damage, whereas DR significantly reduced gene expression related to immune responses, protein quality control, and cellular stress responses. Additionally, our analysis identified key transcription factors (TFs), such as Gata2, Klf16, and Runx3, which likely mediate the gene expression changes observed under DR. These TFs are implicated in critical processes, including signal transduction, transcriptional regulation, and cellular responses to DNA damage. Furthermore, machine learning algorithms identified Gnptg as a key hub gene associated with programmed cell death (PCD) in HSC aging with its gene products maintaining lysosomal homeostasis. DR reduced lysosomal numbers and preserved lysosomal membrane integrity in aging HSCs, suggesting that lysosomal dysfunction contributes to HSC aging. Overall, DR induces a distinct transcriptional landscape in aged HSCs, suggesting a protective role by reducing harmful gene expression linked to inflammation, DNA damage, apoptosis, and stress responses, thereby maintaining HSC function during aging.

饮食限制对老年雌性小鼠造血干细胞转录谱的影响。
本研究探讨了饮食限制(DR)对老年小鼠造血干细胞(hsc)基因表达的影响。从分选的造血干细胞中获得RNA测序(RNA-seq)数据,然后通过加权基因共表达网络分析(WGCNA)鉴定差异表达基因(deg)和关键转录模块。主成分分析(PCA)和热图显示各组之间存在显著差异,突出显示衰老过程中基因表达明显上调,DR下基因表达谱更受抑制。功能富集分析表明,hsc衰老过程的特征是炎症反应和DNA损伤相关基因表达增强,而DR显著降低免疫反应相关基因表达。蛋白质质量控制和细胞应激反应。此外,我们的分析确定了关键转录因子(TFs),如Gata2, Klf16和Runx3,它们可能介导dr下观察到的基因表达变化。这些TFs涉及关键过程,包括信号转导,转录调节和细胞对DNA损伤的反应。此外,机器学习算法确定Gnptg是与HSC衰老过程中程序性细胞死亡(PCD)相关的关键枢纽基因,其基因产物维持溶酶体稳态。DR减少了老化HSC的溶酶体数量,并保留了溶酶体膜的完整性,提示溶酶体功能障碍有助于HSC衰老。总的来说,DR在衰老的HSC中诱导了一个独特的转录景观,表明DR通过减少与炎症、DNA损伤、细胞凋亡和应激反应相关的有害基因表达,从而在衰老过程中维持HSC的功能,从而发挥保护作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Biogerontology
Biogerontology 医学-老年医学
CiteScore
8.00
自引率
4.40%
发文量
54
审稿时长
>12 weeks
期刊介绍: The journal Biogerontology offers a platform for research which aims primarily at achieving healthy old age accompanied by improved longevity. The focus is on efforts to understand, prevent, cure or minimize age-related impairments. Biogerontology provides a peer-reviewed forum for publishing original research data, new ideas and discussions on modulating the aging process by physical, chemical and biological means, including transgenic and knockout organisms; cell culture systems to develop new approaches and health care products for maintaining or recovering the lost biochemical functions; immunology, autoimmunity and infection in aging; vertebrates, invertebrates, micro-organisms and plants for experimental studies on genetic determinants of aging and longevity; biodemography and theoretical models linking aging and survival kinetics.
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