Sca-1 identifies a monocyte-predisposed hierarchy of hematopoietic progenitor cells in the postnatal murine aorta

Activity: Invited talks and oral presentationsInvited Keynote and Plenary Presentations

Description

Hematopoiesis originates from the dorsal aorta during embryogenesis. While adult blood vessels harbor progenitor populations for endothelial and smooth muscle cells, it is not known if they contain hematopoietic stem (HSCs) or progenitor cells (HPCs). Here, we hypothesized that the postnatal murine aorta is a source of HPCs and HSCs. In short- and long-term culture, aortic cells from C57BL/6 mice generated multipotent and lineage-specific hematopoietic colony-forming units (CFUs), with unique preponderance of macrophage CFUs. This clonogenicity was primarily localized to Sca-1+ cells in the adventitia and was enhanced in lesion-free ApoE-/- mice. Expression of Sca-1 in the aorta colocalized with both canonical HSC markers as well as mature leukocyte antigens, notably, Ly-6C. Adoptive transfer of aortic cells conferred a degree of early multilineage hematopoietic reconstitution, with diminution to low but detectable levels of long-term chimerism. Although trafficking from bone marrow was shown to replenish some of the aorta's hematopoietic potential following irradiation, the majority of macrophage precursors appeared to arise locally, suggesting constitutive or long-term residence in the vessel wall. Together these findings show that the postnatal murine aorta contains rare multipotent HSCs/HPCs and is selectively enriched with Sca-1+ monocyte/macrophage precursors. These populations may represent novel, local sources of inflammatory cells.
Period2011
Event titleEarly Career Investigator Finals - Winner, Council of Arteriosclerosis Thrombosis and Vascular Biology, American Heart Association Scientific Sessions Meeting, Orlando, Florida
Event typeConference
LocationUnited States