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Cadmium modulates hematopoietic stem and progenitor cells and skews toward myelopoiesis in mice
Toxicology and Applied Pharmacology, Issue: , Volume: 313, Pages: 24-34. | 2016-01-12
0 Patent citations    2 Scholarly citations     Reference Count: 78
Yandong Zhang;Xinchun Yu;Shuhui Sun;Qian Li;Yunli Xie;Qiang Li;Yifan Zhao;Jianfeng Pei;Wenmin Zhang;Peng Xue;Zhijun Zhou;Yubin Zhang

摘要

Abstract The heavy metal cadmium (Cd) is known to modulate immunity and cause osteoporosis. However, how Cd influences on hematopoiesis remain largely unknown. Herein, we show that wild-type C57BL/6 (B6) mice exposed to Cd for 3 months had expanded bone marrow (BM) populations of long-term hematopoietic stem cells (LT-HSCs), common myeloid progenitors (CMPs) and granulocyte-macrophage progenitors (GMPs), while having reduced populations of multipotent progenitors (MPPs) and common lymphoid progenitors (CLPs). A competitive mixed BM transplantation assay indicates that BM from Cd-treated mice had impaired LT-HSC ability to differentiate into mature cells. In accordance with increased myeloid progenitors and decreased lymphoid progenitors, the BM and spleens of Cd-treated mice had more monocytes and/or neutrophils and fewer B cells and T cells. Cd impaired the ability of the non-hematopoietic system to support LT-HSCs, in that lethally irradiated Cd-treated recipients transplanted with normal BM cells had reduced LT-HSCs after the hematopoietic system was fully reconstituted. This is consistent with reduced osteoblasts, a known critical component for HSC niche, observed in Cd-treated mice. Conversely, lethally irradiated control recipients transplanted with BM cells from Cd-treated mice had normal LT-HSC reconstitution. Furthermore, both control mice and Cd-treated mice that received Alendronate, a clinical drug used for treating osteoporosis, had BM increases of LT-HSCs. Thus, the results suggest Cd increase of LT-HSCs is due to effects on HSCs and not on osteoblasts, although, Cd causes osteoblast reduction and impaired niche function for maintaining HSCs. Furthermore, Cd skews HSCs toward myelopoiesis.


机构

Fudan University;School of Public Health and Key Laboratory of Public Health, MOE, Fudan University, Shanghai 200032, China. Electronic address: yz001@fudan.edu.cn.Fudan University;Insititute of Brain Sciences, Fudan University, Shanghai 200032, China.Fudan University;Key Laboratory of Medical Molecular Virology, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai 200032, China.Fudan University;School of Public Health and Key Laboratory of Public Health, MOE, Fudan University, Shanghai 200032, China.Fudan University;School of Public Health and Key Laboratory of Public Health, MOE, Fudan University, Shanghai 200032, China.Centers for Disease Control and Prevention;Putuo District Center for Disease Control and Prevention, Shanghai 200062, China.Fudan University;School of Public Health and Key Laboratory of Public Health, MOE, Fudan University, Shanghai 200032, China.Fudan University;School of Public Health and Key Laboratory of Public Health, MOE, Fudan University, Shanghai 200032, China.Fudan University;School of Public Health and Key Laboratory of Public Health, MOE, Fudan University, Shanghai 200032, China.Fudan University;School of Public Health and Key Laboratory of Public Health, MOE, Fudan University, Shanghai 200032, China.Fudan University;School of Public Health and Key Laboratory of Public Health, MOE, Fudan University, Shanghai 200032, China.Fudan University;School of Public Health and Key Laboratory of Public Health, MOE, Fudan University, Shanghai 200032, China.


实验动物:

mouse(小鼠)   

科学仪器:

染毒装置   

细胞器官:

progenitor cell    bone    hematopoietic stem cell    macrophage    T cell    B cell   

疾病:

Osteoporosis   

实验试剂:

Alendronate(D019386)    Cadmium(D002104)   

免疫治疗:

Biology    Immunology    Bone marrow    Haematopoiesis    Myeloid    Myelopoiesis   

实验方案:

RNAi Epigenetics & Gene Regulation(RNAi、表观遗传学和基因调控)   

文献类型:

journal article;

出版商:

Academic Press Inc.

发表时间:

2016-01-12

基金信息