2022年3月2日出版的《自然》杂志发表美国斯坦福大学Tony Wyss-Coray、Stephen R. Quake、Andreas Keller课题组的最新成果，他们合作在单细胞分辨率水平揭示了异时共生的分子特征。
研究人员对20个器官进行了单细胞RNA测序，以揭示异时共生过程中年轻和老年血液细胞类型的特异性反应。脂肪间充质基质细胞、造血干细胞和肝细胞属于特别敏感的细胞类型。在信号通路水平，年轻血液除了逆转既定的衰老模式外，还调用了新的基因组，电子传递链亚基的编码基因在全身范围内得到恢复，这表明线粒体功能在异时共生介导再生过程中的重要作用。
研究人员观察到随着年龄的增长，基因表达几乎普遍丧失，这在很大程度上可由异时共生所模拟：老化的血液会降低整体基因表达，而年轻的血液会在选定的细胞类型中恢复它。总之，这些数据为系统理解血源性因子和细胞完整性之间的相互作用奠定了基础。
据介绍，减缓或逆转生物衰老会对降低疾病风险和保持活力产生重大影响。尽管越来越多的干预方法出现成效，但它们对全身不同细胞类型的有效性以及对恢复细胞活力的分子机制却亟待探索。
附：英文原文
Title: Molecular hallmarks of heterochronic parabiosis at single-cell resolution
Author: Plovics, Rbert, Keller, Andreas, Schaum, Nicholas, Tan, Weilun, Fehlmann, Tobias, Borja, Michael, Kern, Fabian, Bonanno, Liana, Calcuttawala, Kruti, Webber, James, McGeever, Aaron, Luo, Jian, Pisco, Angela Oliveira, Karkanias, Jim, Neff, Norma F., Darmanis, Spyros, Quake, Stephen R., Wyss-Coray, Tony
Issue&Volume: 2022-03-02
Abstract: The ability to slow or reverse biological ageing would have major implications for mitigating disease risk and maintaining vitality1. Although an increasing number of interventions show promise for rejuvenation2, their effectiveness on disparate cell types across the body and the molecular pathways susceptible to rejuvenation remain largely unexplored. Here we performed single-cell RNA sequencing on 20 organs to reveal cell-type-specific responses to young and aged blood in heterochronic parabiosis. Adipose mesenchymal stromal cells, haematopoietic stem cells and hepatocytes are among those cell types that are especially responsive. On the pathway level, young blood invokes new gene sets in addition to reversing established ageing patterns, with the global rescue of genes encoding electron transport chain subunits pinpointing a prominent role of mitochondrial function in parabiosis-mediated rejuvenation. We observed an almost universal loss of gene expression with age that is largely mimicked by parabiosis: aged blood reduces global gene expression, and young blood restores it in select cell types. Together, these data lay the groundwork for a systemic understanding of the interplay between blood-borne factors and cellular integrity. A transcriptomics study demonstrates cell-type-specific responses to differentially aged blood and shows young blood to have restorative and rejuvenating effects that may be invoked through enhanced mitochondrial function.
DOI: 10.1038/s41586-022-04461-2
Source: https://www.nature.com/articles/s41586-022-04461-2
Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
官方网址：http://www.nature.com/
投稿链接：http://www.nature.com/authors/submit_manuscript.html
本期文章：《自然》：Online/在线发表
