Loss of Atg7 causes chaotic nucleosome assembly of mouse bone marrow CD11b+Ly6G- myeloid cells

Yixuan Fang; Yue Gu; Lei Li; Lingjiang Zhu; Jiawei Qian; Chen Zhao; Li Xu; Wen Wei; Yanhua Du; Na Yuan; Suping Zhang; Ye Yuan; Youjia Xu; Cizhong Jiang; Jianrong Wang

doi:10.18632/aging.104176

Loss of Atg7 causes chaotic nucleosome assembly of mouse bone marrow CD11b⁺Ly6G^- myeloid cells

Aging (Albany NY). 2020 Nov 24;12(24):25673-25683. doi: 10.18632/aging.104176. Epub 2020 Nov 24.

Authors

Yixuan Fang^{1

2

3

4}, Yue Gu^{1

2}, Lei Li^{1

2}, Lingjiang Zhu^{1

2}, Jiawei Qian¹, Chen Zhao^{1

2}, Li Xu^{1

2}, Wen Wei^{1

2}, Yanhua Du⁵, Na Yuan^{1

2

3

4}, Suping Zhang^{1

2

3

4}, Ye Yuan⁶, Youjia Xu⁶, Cizhong Jiang⁵, Jianrong Wang^{1

2

3

4}

Affiliations

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.

Abstract

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.

Keywords: Atg7; aging; histone H3.1; nucleosome assembly.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antigens, Ly / metabolism*
Autophagy-Related Protein 7 / genetics*
Autophagy-Related Protein 7 / metabolism
Bone Marrow Cells / metabolism
CD11b Antigen / metabolism*
Mice
Mice, Knockout
Myeloid Cells / metabolism*
Nucleosomes / metabolism*

Substances

Antigens, Ly
CD11b Antigen
Ly6G antigen, mouse
Nucleosomes
Autophagy-Related Protein 7