Figure 2.

Potential origins and trafficking of fibrocytes. This diagram shows potential fibrocyte precursors and sites of differentiation. In addition, it shows the trafficking of fibrocytes as well as Col1+ macrophages that do not express collagen that could account for the identification of Col1+ hematopoietic-derived cells within the bone marrow, blood, spleen, and in peripheral tissues. Fibrocytes may differentiate from a dedicated precursor within the bone marrow before being released into the circulation. Alternatively, fibrocytes may instead differentiate from monocytes or macrophages. Classical monocytes are continuously generated by hematopoiesis in the bone marrow and are released into the circulation. Most monocytes leave the circulation to enter a particular tissue as classical monocytes, but some are retained and differentiate into non-classical monocytes. While limited evidence suggests that classical monocytes do not directly differentiate into fibrocytes, non-classical monocytes, monocyte-derived macrophages, and tissue resident macrophages may be possible fibrocyte precursors. In addition, like tissue resident macrophages there may also exist a tissue resident population of fibrocytes established early in development. Both fibrocytes and Col1+ macrophages may reenter the circulation through the lymphatic system allowing them to traffic to the spleen or bone marrow. Differentiation of monocytes and macrophages into fibrocytes may also occur in the spleen and/or splenic fibrocytes may have extra-splenic origins. Potential origins of fibrocytes in the bone marrow (red), tissue (blue), and spleen (green) are identified by the solid-colored bubbles. The arrows are color-coded to identify the directional trafficking of each population and the potential for each cell population to be present outside of their anatomical compartment of origin is indicated by bubbles outlined in the color according to the location of origin. For example, spleen-derived fibrocytes may reenter the circulation directly or indirectly through the lymphatic system. Once in the circulation, spleen-derived fibrocytes may then traffic to the bone marrow or another tissue. bone marrow (BM), Col1 immunolabeled (Col1+), monocyte (Mo.), macrophage (Mφ), peripheral blood mononuclear cells (PBMCs).