Identification of a Monocyte-Predisposed Hierarchy of Hematopoietic Progenitor Cells in the Adventitia of Postnatal Murine Aorta
Background—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 progenitor (HPCs) or stem cells (HSCs). Here, we hypothesized that the arterial wall is a source of HPCs and HSCs in postnatal life.
Methods and Results—Single cell aortic disaggregates were prepared from adult chow-fed C57BL/6 and ApoE-/- mice. In short- and long-term methylcellulose-based culture, aortic cells generated a broad spectrum of multipotent and lineage-specific hematopoietic colony-forming units (CFUs), with preponderance of macrophage CFUs (CFU-M). This clonogenicity was higher in lesion-free ApoE-/- mice and primarily localized to Sca-1+ cells in the adventitia. Expression of Sca-1 in the aorta co-localized with canonical HSC markers, as well as CD45 and mature leukocyte antigens. Adoptive transfer of labeled aortic cells from GFP transgenic donors to irradiated C57BL/6 recipients confirmed content of rare HSCs (1 per 4,000,000 cells), capable of self-renewal and durable, low level reconstitution of leukocytes. Moreover, the predominance of long-term macrophage precursors was evident by late recovery of GFP+ colonies from recipient bone marrow and spleen that were exclusively CFU-M. 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 long-term residence in the vessel wall.
Conclusions—The postnatal murine aorta contains rare multipotent HPCs/HSCs and is selectively enriched with Sca-1+ monocyte/macrophage precursors. These populations may represent novel, local vascular sources of inflammatory cells.
- Received August 1, 2011.
- Accepted November 4, 2011.
- Copyright © 2011, American Heart Association, Inc. All rights reserved. Unauthorized use prohibited