Department of Human Genetics, McGill University, 3640 rue University, Montréal, QC, H3A 0C7, Canada.
Lady Davis Institute for Medical Research, Jewish General Hospital, 3755 Chemin de la Côte-Sainte-Catherine, Montréal, QC, H3T 1E2, Canada.
Nat Commun. 2023 Feb 1;14(1):535. doi: 10.1038/s41467-023-36265-x.
Adult stem cells are indispensable for tissue regeneration, but their function declines with age. The niche environment in which the stem cells reside plays a critical role in their function. However, quantification of the niche effect on stem cell function is lacking. Using muscle stem cells (MuSC) as a model, we show that aging leads to a significant transcriptomic shift in their subpopulations accompanied by locus-specific gain and loss of chromatin accessibility and DNA methylation. By combining in vivo MuSC transplantation and computational methods, we show that the expression of approximately half of all age-altered genes in MuSCs from aged male mice can be restored by exposure to a young niche environment. While there is a correlation between gene reversibility and epigenetic alterations, restoration of gene expression occurs primarily at the level of transcription. The stem cell niche environment therefore represents an important therapeutic target to enhance tissue regeneration in aging.
成体干细胞对于组织再生是不可或缺的，但它们的功能会随着年龄的增长而下降。干细胞所处的微环境在其功能中起着关键作用。然而，目前缺乏对微环境影响干细胞功能的定量分析。我们以肌肉干细胞（MuSC）作为模型，发现衰老会导致其亚群的转录组发生显著变化，伴随着染色质可及性和 DNA 甲基化的局部获得和丧失。通过体内 MuSC 移植和计算方法相结合，我们发现大约一半的衰老雄性小鼠 MuSCs 中发生改变的基因的表达可以通过暴露于年轻的微环境来恢复。虽然基因的可逆性和表观遗传改变之间存在相关性，但基因表达的恢复主要发生在转录水平。因此，干细胞微环境是增强衰老组织再生的一个重要治疗靶点。
