Research Paper Volume 12, Issue 24 pp 25673—25683
Loss of Atg7 causes chaotic nucleosome assembly of mouse bone marrow CD11b+Ly6G- myeloid cells
- 1 Hematology Center of Cyrus Tang Medical Institute, Soochow University School of Medicine, Suzhou 215123, China
- 2 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
- 3 Department of Hematopoietic Engineering, Susky Life SciTech (Suzhou) Co. Ltd., Suzhou 215124, China
- 4 State Key Laboratory of Radiation Medicine and Radioprotection, Soochow University School of Medicine, Suzhou 215123, China
- 5 Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education, Orthopaedic Department of Tongji Hospital, the School of Life Sciences and Technology, Shanghai Key Laboratory of Signaling and Disease Research, Tongji University, Shanghai 200092, China
- 6 Department of Orthopaedics, the Second Affiliated Hospital of Soochow University, Osteoporosis Institute of Soochow University, Suzhou 215004, China
Received: June 19, 2020 Accepted: August 15, 2020 Published: November 24, 2020https://doi.org/10.18632/aging.104176
How to Cite
Copyright: © 2020 Fang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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.