Loss of Atg77 causes chaotic nucleosome assembly of mouse bone marrow CD11b(+)Ly6G(-) myeloid cells

摘要

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 CD11b(+)Ly6G(+) and CD11b(+)Ly6G(-) populations in mouse bone marrow.Surprisingly, Atg7 deletion causes abnormally accumulated histone H3.1 to be overwhelmingly trapped in the cytoplasm in the CD11b(+)Ly6G(-), but not the CD11b(+)Ly6G(+) compartment. RNA profiling revealed extensively chaotic expression of the genes required in nucleosome assembly. Functional assays further indicated upregulated aging markers in the CD11b(+)Ly6G(-) population. Therefore, our study suggests that Atg7 is essential for maintaining proper nucleosome assembly and limiting aging in the bone marrow CD11b(+)Ly6G(-) population.