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. Although adult blood vessels harbor progenitor populations for endothelial and smooth muscle cells, it is not known if they contain hematopoietic progenitor or stem cells. Here, we hypothesized that the arterial wall is a source of hematopoietic progenitor and stem cells in postnatal life.


RESULTS
Single-cell aortic disaggregates were prepared from adult chow-fed C57BL/6 and apolipoprotein E-null (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, with a preponderance of macrophage colony-forming units. This clonogenicity was higher in lesion-free ApoE(-/-) mice and localized primarily to stem cell antigen-1-positive cells in the adventitia. Expression of stem cell antigen-1 in the aorta colocalized with canonical hematopoietic stem cell markers, as well as CD45 and mature leukocyte antigens. Adoptive transfer of labeled aortic cells from green fluorescent protein transgenic donors to irradiated C57BL/6 recipients confirmed the content of rare hematopoietic stem cells (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 green fluorescent protein-positive colonies from recipient bone marrow and spleen that were exclusively macrophage colony-forming units. Although trafficking from bone marrow was shown to replenish some of the hematopoietic potential of the aorta after 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 hematopoietic progenitor/stem cells and is selectively enriched with stem cell antigen-1-positive monocyte/macrophage precursors. These populations may represent novel, local vascular sources of inflammatory cells.
Division of Cardiovascular Diseases, Mayo Clinic, 200 First St SW, Rochester, MN 55905, USA.
Peter J
PJ
Psaltis
Adriana
A
Harbuzariu
Sinny
S
Delacroix
Tyra A
TA
Witt
Eric W
EW
Holroyd
Daniel B
DB
Spoon
Scott J
SJ
Hoffman
Shuchong
S
Pan
Laurel S
LS
Kleppe
Cheryl S
CS
Mueske
Rajiv
R
Gulati
Gurpreet S
GS
Sandhu
Robert D
RD
Simari
D019264:Adoptive Transfer; D000818:Animals; D000950:Antigens, Ly / Q000378:metabolism; D001011:Aorta / Q000166:cytology* / Q000254:growth & development*; D001057:Apolipoproteins E / Q000235:genetics; D015415:Biomarkers / Q000378:metabolism; D016026:Bone Marrow Transplantation; D019070:Cell Lineage / Q000276:immunology; D004730:Endothelium, Vascular / Q000166:cytology / Q000254:growth & development; D049452:Green Fluorescent Proteins / Q000235:genetics; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000276:immunology*; D016130:Immunophenotyping; D008264:Macrophages / Q000166:cytology; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009000:Monocytes / Q000166:cytology*; D039902:Multipotent Stem Cells / Q000166:cytology / Q000276:immunology; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000254:growth & development; D018183:Transplantation Chimera; D014916:Whole-Body Irradiation
D000950:Antigens, Ly; D001057:Apolipoproteins E; D015415:Biomarkers; C074650:Ly6a protein, mouse; D008565:Membrane Proteins; D049452:Green Fluorescent Proteins