A Lineage of Myeloid Cells Independent of Myb and Hematopoietic Stem Cells

Abstract

<jats:p>Macrophages and dendritic cells (DCs) are key components of cellular immunity and are thought to originate and renew from hematopoietic stem cells (HSCs). However, some macrophages develop in the embryo before the appearance of definitive HSCs. We thus reinvestigated macrophage development. We found that the transcription factor Myb was required for development of HSCs and all CD11b<jats:sup>high</jats:sup>monocytes and macrophages, but was dispensable for yolk sac (YS) macrophages and for the development of YS-derived F4/80<jats:sup>bright</jats:sup>macrophages in several tissues, such as liver Kupffer cells, epidermal Langerhans cells, and microglia—cell populations that all can persist in adult mice independently of HSCs. These results define a lineage of tissue macrophages that derive from the YS and are genetically distinct from HSC progeny.</jats:p>

Microglia and Monocyte-Derived Macrophages in Stroke

“…Microglial precursors express CX3CR1 and CD45 and travel to the neuroectoderm in a matrix metalloproteinase-8-and matrix metalloproteinase-9-dependent manner [36,38]. Importantly, these are not exchanged with fetal liver or bone marrowderived hematopoietic stem cells and they possess selfrenewing capability under physiologic conditions [35,36,39,40]. The morphology and protein expression of microglia are not uniform, and this heterogeneity could explain differential microglial responses in different surroundings [41,42].…”

Monocytes and Macrophages in Cancer: Development and Functions

“…The identification of additional markers or progenitors specific for M-MDSCs (compared to normal monocytes) will certainly help elucidating this issue. [113][114][115], whereas relative levels of F4/80 and CD11b may discriminate between monocyte-derived macrophages and yolk sac-derived macrophages (such as Kupffer cells in liver, Langerhans' cells in skin or microglia in brain) [2]. For Mo-DC, markers for discrimination from other DC-subsets have been identified, such as DC-SIGN for DCs in inflamed lymph nodes [48], CX3CR1 for intestinal lamina propia DCs [52] and TNF-α/ROS-production for Tip-DCs [116,117] …”

“…The mononuclear phagocyte system (MPS) represents a body-wide, specialized system of different phagocytic cell types derived from bone marrow and yolk sac progenitors [1,2]. Monocytes (Mo) and macrophages (MΦ) are essential components of the MPS and critically involved in central processes of the MPS such as innate immune functions, support of adaptive immunity and tissue homeostasis [1,3].…”

“…As a second origin, it has recently been reported that yolk sac-derived cells can constitute a different line of macrophages in adult mice. Their development occurs independently of monocytes derived from adult hematopoietic stem cells (HSC) and the transcription factor Myb [2].…”

A short history of hemogenic endothelium

“…Shortly after the formation of primitive erythrocytes, multi-potent and lineage-restricted hematopoietic progenitor cells that display adult-type morphology are generated asynchronously in different hematopoietic sites of the embryo (reviewed in [6,7]), including the yolk sac, para-aortic splanchnopleura (PAS)/ aorta-gonad-mesonephros (AGM) region, vitelline and umbilical arteries, placenta, and most recently recognized, the heart [8]. These progenitors are generally considered transient in nature as also they emerge in the absence of adult HSC activity, though some specific lymphoid and myeloid cells may persist into adulthood [9][10][11]. It is the yolk sac that provides most, if not all, of the hematopoietic progenitor cells that seed the fetal liver at E10.…”