A lineage of myeloid cells independent of Myb and hematopoietic stem cells
22.03.2012
Schulz C, Gomez Perdiguero E, Chorro L, Szabo-Rogers H, Cagnard N, Kierdorf K, Prinz M, Wu B, Jacobsen SE, Pollard JW, Frampton J, Liu KJ, Geissmann F
Science. 2012 Apr 6;336(6077):86-90
Hematopoietic stem cells (HSCs) from the fetal liver, and later the bone marrow, give rise to leucocytes, including macrophages and dendritic cells (DC). Accordingly, we found that embryos deficient in the transcription factor Myb, which lack HSC-derived hematopoietic cells, also lack all CD11bhigh tissue macrophages. However, yolk sac (YS) macrophages developed normally in Myb-/- mice, colonized the embryo, and differentiated into F4/80bright CD11blow CX3CR1high macrophages and DCs in the skin, spleen, pancreas, lung, liver, kidney, and brain. In the skin, F4/80bright CX3CR1high YS-derived macrophages are the precursors of epidermal Langerhans cells (LC), that retain self renewal capacity. Both Myb-dependent HSC-derived and Myb-independent YS-derived F4/80bright macrophages require the transcription factor Pu.1 for their development. Our data therefore define a lineage of YS-derived, Pu.1–dependent but Myb–
independent, F4/80bright tissue macrophages and DC, genetically distinct from HSCs, and exemplified by epidermal LC and pancreas b-islet macrophages.
