Tissue resident macrophages have very significant roles under both physiological and pathological conditions. For a long time, it was well-accepted that adult mammalian tissue resident macrophages were derived from monocytes generated by hematopoietic stem cells (HSCs) in the bone marrow. However, recent fate mapping analysis with the Cre/loxP labelling system showed that a large population of macrophages were derived from embryonic progenitors generated in the yolk sac of mice embryos. These macrophages can proliferate locally in different organs to maintain themselves. Thus, the origins of tissue resident macrophages are still debatable. Multiple origins, including primitive macrophages, erythro-myeloid progenitors (EMPs) and HSCs may exist. Due to the limitations of fate mapping tech...[ Read more ]

Tissue resident macrophages have very significant roles under both physiological and pathological conditions. For a long time, it was well-accepted that adult mammalian tissue resident macrophages were derived from monocytes generated by hematopoietic stem cells (HSCs) in the bone marrow. However, recent fate mapping analysis with the Cre/loxP labelling system showed that a large population of macrophages were derived from embryonic progenitors generated in the yolk sac of mice embryos. These macrophages can proliferate locally in different organs to maintain themselves. Thus, the origins of tissue resident macrophages are still debatable. Multiple origins, including primitive macrophages, erythro-myeloid progenitors (EMPs) and HSCs may exist. Due to the limitations of fate mapping technology in mice, the origin of macrophages in different organs is still an open question.

Similar to mammals, zebrafish also have different waves of hematopoiesis which can generate primitive macrophages, EMPs and HSCs respectively. These waves of hematopoiesis take place in different hematopoietic origins in zebrafish, including the rostral blood island (RBI), the posterior blood island (PBI) and the ventral wall of dorsal aorta (VDA). Taking advantage of the transparent appearance of zebrafish embryos, we have utilized an IR-LEGO-CreER-loxP system which can specifically label hematopoietic progenitors generated from different hematogenic origins. This fate mapping system is more precise than previous fate mapping conducted in mice as it has both temporal and spatial resolution. Using this system, we find that most embryonic macrophages in zebrafish are derived from RBI. These RBI-derived macrophages will be gradually replaced by VDA-derived macrophages, and VDA is the main source of adult macrophages. These adult macrophages, probably with the exception of microglia, are likely to be generated by HSCs. These results from this novel fate mapping analysis technology give a comprehensive understanding about the origins of tissue resident macrophages, and may help to clarify the confusion in the field currently.