Abstract 13460: Sca-1 Identifies a Monocyte-Predisposed Hierarchy of Hematopoietic Progenitor Cells in the 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 still contain hematopoietic stem (HSCs) and progenitor cells (HPCs). This study hypothesized that the vasculature is a source of HSCs/HPCs in postnatal life.
Methods and Results Single cell aortic disaggregates were prepared from adult C57BL/6 and chow-fed ApoE-/- mice. In short- and long-term methylcellulose-based culture, aortic cells generated a broad spectrum of multipotent and lineage-specific colony-forming units (CFUs), with unique preponderance of macrophage CFUs (CFU-M). This clonogenicity was higher in ApoE-/- mice and primarily localized to Sca-1+ cells in the adventitia. Sca-1 was co-expressed both with canonical HSC markers (c-kit, CD150, CD34) and mature myeloid and lymphoid antigens. Unlike in bone marrow (BM) or blood, the Sca-1+ phenotype in aorta also encompassed the majority of cells expressing the monocyte marker, Ly-6C, and c-fms (CD115), the receptor for M-CSF. Transfer of aortic cells from GFP donors into irradiated wildtype mice 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 BM and spleen that were exclusively CFU-M. The source of vascular CFU capacity was assessed by tracking GFP+ BM cells in the vessel walls of irradiated C57BL/6 and ApoE-/- mice. Donor cells engrafted progressively within the adventitia to a greater extent in ApoE-/- mice. Aortic CFUs were of mixed origin, with BM-derived cells accounting for 78% of multilineage and non-M colonies after six months, but only 17% of CFU-M.
Conclusion The postnatal murine aorta contains a rare population of multipotent HSCs/HPCs. In addition, the vascular wall is selectively enriched with Sca-1+ monocyte/macrophage precursors that are predominantly constitutive or long-term resident in the adventitia. These populations may represent novel, local sources of inflammatory cells that participate in vascular remodeling and disease.
- © 2011 by American Heart Association, Inc.