title: Cadmium modulates hematopoietic stem and progenitor cells and skews toward myelopoiesis in mice.
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 3months 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.
authors: School of Public Health and Key Laboratory of Public Health, MOE, Fudan University, Shanghai 200032, China.
authors: Yandong
authors: Y
authors: Zhang
authors: School of Public Health and Key Laboratory of Public Health, MOE, Fudan University, Shanghai 200032, China.
authors: Xinchun
authors: X
authors: Yu
authors: Key Laboratory of Medical Molecular Virology, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai 200032, China.
authors: Shuhui
authors: S
authors: Sun
authors: School of Public Health and Key Laboratory of Public Health, MOE, Fudan University, Shanghai 200032, China.
authors: Qian
authors: Q
authors: Li
authors: Insititute of Brain Sciences, Fudan University, Shanghai 200032, China.
authors: Yunli
authors: Y
authors: Xie
authors: Putuo District Center for Disease Control and Prevention, Shanghai 200062, China.
authors: Qiang
authors: Q
authors: Li
authors: School of Public Health and Key Laboratory of Public Health, MOE, Fudan University, Shanghai 200032, China.
authors: Yifan
authors: Y
authors: Zhao
authors: School of Public Health and Key Laboratory of Public Health, MOE, Fudan University, Shanghai 200032, China.
authors: Jianfeng
authors: J
authors: Pei
authors: School of Public Health and Key Laboratory of Public Health, MOE, Fudan University, Shanghai 200032, China.
authors: Wenmin
authors: W
authors: Zhang
authors: School of Public Health and Key Laboratory of Public Health, MOE, Fudan University, Shanghai 200032, China.
authors: Peng
authors: P
authors: Xue
authors: School of Public Health and Key Laboratory of Public Health, MOE, Fudan University, Shanghai 200032, China.
authors: Zhijun
authors: Z
authors: Zhou
authors: School of Public Health and Key Laboratory of Public Health, MOE, Fudan University, Shanghai 200032, China. Electronic address: yz001@fudan.edu.cn.
authors: Yubin
authors: Y
authors: Zhang
mesh_terms: D019386:Alendronate / Q000494:pharmacology; D000818:Animals; D001822:Body Burden; D001842:Bone and Bones / Q000166:cytology / Q000187:drug effects; D002104:Cadmium / Q000493:pharmacokinetics / Q000633:toxicity*; D006412:Hematopoietic Stem Cells / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D038042:Myelopoiesis / Q000187:drug effects*; D010006:Osteoblasts / Q000187:drug effects; D013234:Stem Cells / Q000187:drug effects*
chemical_list: D002104:Cadmium; D019386:Alendronate
keywords: Cadmium; Hematopoiesis; Hematopoietic stem and progenitor cells; Myelopoiesis