Toxic Effects of Cobalt on Erythroid Progenitor Cells

Cobalt is a crucial trace element that widely exists in natural environments and is necessary for normal physiological function. However, excessive cobalt exposure leads to various adverse health effects, especially hematological and endocrine dysfunctions. Here, we investigated the toxicity of cobalt on early erythropoiesis by using ex vivo cultured erythroid progenitor cells (EPCs). We exposed EPCs to cobalt chloride (CoCl2) and observed that their proliferation was significantly reduced after treatment with 50 mu M CoCl2 for 3 days and 10 mu M CoCl2 for 4 days. Furthermore, CoCl2 exposure reduced the proportion of S phase cells and induced apoptosis of EPCs in a dose-dependent manner (20-100 mu M). Notably, further studies revealed that CoCl2 exposure inhibited the expression and phosphorylation of the erythroid proliferation master gene c-Kit. During EPC differentiation, treatment with CoCl2 hindered the enucleation of erythrocytes. Consistent with these findings, the RNA-seq results revealed that CoCl2 treatment inhibited the expression of several genes related to both proliferation and differentiation. The gene responsible for nucleoprotein export during enucleation, Xpo7, was also downregulated. Gene ontology analysis revealed that CoCl2 treatment inhibited a variety of biological processes, including DNA replication and ribosome synthesis. In summary, we demonstrated that sustained excessive CoCl2 exposure impaired the function of the EPCs.