Identity Noise and Adipogenic Traits Characterize Dermal Fibroblast Aging
Identity Noise and Adipogenic Traits Characterize Dermal Fibroblast Aging
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DOI：
10.1016/j.cell.2018.10.012
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发表时间：
2018-11-29
期刊：
影响因子：
64.5
通讯作者：
Aznar Benitah, Salvador
中科院分区：
文献类型：
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作者：
Claudia Salzer, Marion;Lafzi, Atefeh;Aznar Benitah, Salvador
在衰老过程中，基质功能被认为是受损的，但很少有人知道这是否源于成纤维细胞的变化。使用群体和单细胞转录组学，以及长期的谱系追踪，我们研究了在影响寿命的不同饮食制度下，小鼠皮肤成纤维细胞在生理衰老过程中是否发生了变化。我们发现，老年成纤维细胞的身份变得不明确，与年轻皮肤中存在的成纤维细胞状态不再明确划分。此外，老年成纤维细胞不仅减少参与细胞外基质形成的基因的表达，而且还获得成脂性状，矛盾的是变得更类似于新生儿前成脂成纤维细胞。这些改变对全身代谢变化很敏感：长期的热量限制可逆地阻止了它们，而高脂肪饮食则加强了它们。因此，我们的研究结果强调细胞身份的丧失和脂肪形成性状的获得是细胞衰老的一种机制，这是受全身代谢的影响。
During aging, stromal functions are thought to be impaired, but little is known whether this stems from changes of fibroblasts. Using population- and single-cell transcriptomics, as well as long-term lineage tracing, we studied whether murine dermal fibroblasts are altered during physiological aging under different dietary regimes that affect longevity. We show that the identity of old fibroblasts becomes undefined, with the fibroblast states present in young skin no longer clearly demarcated. In addition, old fibroblasts not only reduce the expression of genes involved in the formation of the extracellular matrix, but also gain adipogenic traits, paradoxically becoming more similar to neonatal pro-adipogenic fibroblasts. These alterations are sensitive to systemic metabolic changes: long-term caloric restriction reversibly prevents them, whereas a high-fat diet potentiates them. Our results therefore highlight loss of cell identity and the acquisition of adipogenic traits as a mechanism underlying cellular aging, which is influenced by systemic metabolism.