Hematology Center of Cyrus Tang Medical Institute, Soochow University School of Medicine, Suzhou 215123, China.
National Clinical Research Center for Hematologic Diseases, Collaborative Innovation Center of Hematology, Jiangsu Institute of Hematology, Institute of Blood and Marrow Transplantation, Department of Hematology, The First Affiliated Hospital of Soochow University, Suzhou 215006, China.
Aging (Albany NY). 2020 Nov 24;12(24):25673-25683. doi: 10.18632/aging.104176.
Atg7, a critical component of autophagy machinery, is essential for counteracting hematopoietic aging. However, the non-autophagic role of Atg7 on hematopoietic cells remains fundamentally unclear. In this study, we found that loss of Atg7, but not Atg5, another autophagy-essential gene, in the hematopoietic system reduces CD11b myeloid cellularity including CD11bLy6G and CD11bLy6G populations in mouse bone marrow. Surprisingly, Atg7 deletion causes abnormally accumulated histone H3.1 to be overwhelmingly trapped in the cytoplasm in the CD11bLy6G, but not the CD11bLy6G compartment. RNA profiling revealed extensively chaotic expression of the genes required in nucleosome assembly. Functional assays further indicated upregulated aging markers in the CD11bLy6G population. Therefore, our study suggests that Atg7 is essential for maintaining proper nucleosome assembly and limiting aging in the bone marrow CD11bLy6G population.
Atg7 是自噬机制的关键组成部分,对于对抗造血衰老至关重要。然而,Atg7 在造血细胞上的非自噬作用在根本上仍不清楚。在这项研究中,我们发现造血系统中 Atg7 的缺失(而非另一个自噬必需基因 Atg5)会减少骨髓中 CD11b 髓样细胞的数量,包括 CD11bLy6G 和 CD11bLy6G 群体。令人惊讶的是,Atg7 的缺失导致异常积累的组蛋白 H3.1 几乎完全被困在 CD11bLy6G 细胞的细胞质中,而不是在 CD11bLy6G 区室中。RNA 谱分析显示核小体组装所需基因的表达广泛混乱。功能测定进一步表明 CD11bLy6G 群体中的衰老标志物上调。因此,我们的研究表明,Atg7 对于维持骨髓 CD11bLy6G 群体中适当的核小体组装和限制衰老至关重要。