单细胞中的表观遗传年龄分析。
Profiling epigenetic age in single cells.
机构信息
Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
出版信息
Nat Aging. 2021 Dec;1(12):1189-1201. doi: 10.1038/s43587-021-00134-3. Epub 2021 Dec 9.
DNA methylation dynamics emerged as a promising biomarker of mammalian aging, with multivariate machine learning models ('epigenetic clocks') enabling measurement of biological age in bulk tissue samples. However, intrinsically sparse and binarized methylation profiles of individual cells have so far precluded the assessment of aging in single-cell data. Here, we introduce , a statistical framework for epigenetic age profiling at single-cell resolution, and validate our approach in mice. Our method recapitulates the chronological age of tissues, while uncovering heterogeneity among cells. We show accurate tracking of the aging process in hepatocytes, demonstrate attenuated epigenetic aging in muscle stem cells, and track age dynamics in embryonic stem cells. We also use to reveal, at the single-cell level, a natural and stratified rejuvenation event occurring during early embryogenesis. We provide our framework as a resource to enable exploration of epigenetic aging trajectories at single-cell resolution.
DNA 甲基化动态成为哺乳动物衰老的有前途的生物标志物,多元机器学习模型(“表观遗传时钟”)能够在批量组织样本中测量生物年龄。然而,单个细胞中固有稀疏和二值化的甲基化谱迄今为止阻止了单细胞数据中衰老的评估。在这里,我们引入了一种用于单细胞分辨率下的表观遗传年龄分析的统计框架,并在小鼠中验证了我们的方法。我们的方法再现了组织的时间年龄,同时揭示了细胞间的异质性。我们在肝细胞中准确地跟踪了衰老过程,证明了肌肉干细胞中表观遗传衰老的减弱,并跟踪了胚胎干细胞中的年龄动态。我们还使用 来揭示在单细胞水平上发生在早期胚胎发生过程中的自然和分层的再生事件。我们提供了我们的框架,以能够在单细胞分辨率下探索表观遗传衰老轨迹。
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