We surveyed 16 published and unpublished data sets to determine whether a consistent pattern of transcriptional deregulation in aging murine hematopoietic stem cells (HSC) exists. Despite substantial heterogeneity between individual studies, we uncovered a core and robust HSC aging signature. We detected increased transcriptional activation in aged HSCs, further confirmed by chromatin accessibility analysis. Unexpectedly, using two independent computational approaches, we established that deregulated aging genes consist largely of membrane-associated transcripts, including many cell surface molecules previously not associated with HSC biology. We show that Selp, the most consistent deregulated gene, is not merely a marker for aged HSCs but is associated with HSC functional decline. Additionally, single-cell transcriptomics analysis revealed increased heterogeneity of the aged HSC pool. We identify the presence of transcriptionally 'young-like' HSCs in aged bone marrow. We share our results as an online resource and demonstrate its utility by confirming that exposure to sympathomimetics, and deletion of Dnmt3a/b, molecularly resembles HSC rejuvenation or aging, respectively.

中文翻译：

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小鼠造血干细胞衰老的全面转录组签名

我们调查了16个已发布和未发布的数据集，以确定在衰老的小鼠造血干细胞（HSC）中是否存在一致的转录失调模式。尽管各个研究之间存在很大的异质性，但我们发现了核心且稳健的HSC衰老特征。我们检测到老年HSCs中转录激活的增加，并通过染色质可及性分析进一步证实。出乎意料的是，使用两种独立的计算方法，我们确定了衰老基因的失控主要由膜相关的转录本组成，包括许多以前与HSC生物学无关的细胞表面分子。我们显示Selp，最一致的失控基因，不仅是老年HSC的标志物，而且与HSC功能下降有关。此外，单细胞转录组学分析显示，老年HSC库的异质性增加。我们鉴定出在老年骨髓中存在转录“年轻样” HSC。我们作为在线资源共享我们的结果，并通过确认暴露于拟交感神经素和Dnmt3a / b的缺失分别在分子上类似于HSC复兴或衰老来证明其效用。