Monocytes are cells of the myeloid lineage that originate from hematopoietic stem cells in the bone marrow. In response to macrophage colony-stimulating factor (M-CSF), progenitor cells differentiate into monoblasts and then pro-monocytes, which enter the bloodstream as monocytes. In mice, circulating monocytes can be classified into two distinct populations based on the expression of specific cell surface markers, inflammatory monocytes and resident monocytes. Murine inflammatory monocytes are defined as CCR2+, CX3CR1low and GR1+ (also know as Ly6). In contrast, resident monocytes in mice are classified as CCR2-, CX3CR1high and GR1-. However, the heterogeneity of circulating human monocytes is not completely understood. Human monocytes that are CD14highCD16- are considered classical monocytes, whereas CD14+CD16+ cells are non-classical monocytes. Circulating monocytes migrate to tissue where they replenish tissue-specific macrophage populations (i.e. osteoclasts, microglia cells, histiocytes, and Kupffer cells).