Oncotarget

Research Papers:

APC/C is essential for hematopoiesis and impaired in aplastic anemia

Jia Wang, Min-Zhi Yin, Ke-Wen Zhao, Fang Ke, Wen-Jie Jin, Xiao-Lin Guo, Tian-Hui Liu, Xiao-Ye Liu, Hao Gu, Xiao-Min Yu, Zhen Li, Li-Li Mu, Deng-Li Hong, Jing Chen and Guo-Qiang Chen _

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Oncotarget. 2017; 8:63360-63369. https://doi.org/10.18632/oncotarget.18808

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Abstract

Jia Wang1,*, Min-Zhi Yin2,*, Ke-Wen Zhao1,*, Fang Ke1,*, Wen-Jie Jin3, Xiao-Lin Guo1, Tian-Hui Liu1, Xiao-Ye Liu1, Hao Gu1, Xiao-Min Yu1, Zhen Li1, Li-Li Mu1, Deng-Li Hong1, Jing Chen4 and Guo-Qiang Chen1

1Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Department of Pathophysiology, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai, 200025, China

2Department of Pathology, Shanghai Children’s Medical Center, SJTU-SM, Shanghai, 200025, China

3Department of Orthopaedics, Shanghai Ninth People's Hospital, SJTU-SM, Shanghai, 200025, China

4Key Laboratory of Pediatric Hematology and Oncology Ministry of Health, Department of Hematology and Oncology, Shanghai Children’s Medical Center, SJTU-SM, Shanghai, 200127, China

*These authors have contributed equally to this work

Correspondence to:

Guo-Qiang Chen, email: [email protected]

Jing Chen, email: [email protected]

Deng-Li Hong, email: [email protected]

Keywords: anaphase promoting complex/cyclosome (APC/C), Anapc2, hematopoietic stem and progenitor cells (HSPCs), dormant HPSCs, aplastic anemia

Received: November 22, 2016     Accepted: June 02, 2017     Published: June 28, 2017

ABSTRACT

Anaphase promoting complex/cyclosome (APC/C) is essential for cell cycle progression. Recently, its non-mitotic functions were also reported but less studied in several tissues including hematopoietic cells. Here, we developed an inducible Anapc2 (a core subunit of APC/C) knockout mice. The animals displayed a fatal bone marrow failure within 7 days after knockout induction. Their hematopoietic stem and progenitor cells (HSPCs) demonstrated a sharp decline and could form little colony. Further, the results of BrdU label-retaining cell assay showed that the dormant HPSCs lost rapidly. Analysis of cell cycle regulators, Skp2, P27, Cdk2, and Cyclin E1, suggested that these quiescent stem cells underwent a shift from quiescence to mitosis followed by apoptosis. We next detected Anapc2-expression in the CD34+ HSPCs of patients with aplastic anemia. CD34+ cells were markedly decreased in the bone marrow and Anapc2-expression in the residual CD34+ cells was undetectable, suggesting that APC/C was deficient and might have a relationship with the pathogenesis of aplastic anemia.


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