title: Characterization of a resident population of adventitial macrophage progenitor cells in postnatal vasculature.
abstract: BACKGROUND
  Macrophages regulate blood vessel structure and function in health and disease. The origins of tissue macrophages are diverse, with evidence for local production and circulatory renewal.
  
  
  OBJECTIVE
  We identified a vascular adventitial population containing macrophage progenitor cells and investigated their origins and fate.
  
  
  RESULTS
  Single-cell disaggregates from adult C57BL/6 mice were prepared from different tissues and tested for their capacity to form hematopoietic colony-forming units. Aorta showed a unique predilection for generating macrophage colony-forming units. Aortic macrophage colony-forming unit progenitors coexpressed stem cell antigen-1 and CD45 and were adventitially located, where they were the predominant source of proliferating cells in the aortic wall. Aortic Sca-1(+)CD45(+) cells were transcriptionally and phenotypically distinct from neighboring cells lacking stem cell antigen-1 or CD45 and contained a proliferative (Ki67(+)) Lin(-)c-Kit(+)CD135(-)CD115(+)CX3CR1(+)Ly6C(+)CD11b(-) subpopulation, consistent with the immunophenotypic profile of macrophage progenitors. Adoptive transfer studies revealed that Sca-1(+)CD45(+) adventitial macrophage progenitor cells were not replenished via the circulation from bone marrow or spleen, nor was their prevalence diminished by depletion of monocytes or macrophages by liposomal clodronate treatment or genetic deficiency of macrophage colony-stimulating factor. Rather adventitial macrophage progenitor cells were upregulated in hyperlipidemic ApoE(-/-) and LDL-R(-/-) mice, with adventitial transfer experiments demonstrating their durable contribution to macrophage progeny particularly in the adventitia, and to a lesser extent the atheroma, of atherosclerotic carotid arteries.
  
  
  CONCLUSIONS
  The discovery and characterization of resident vascular adventitial macrophage progenitor cells provides new insight into adventitial biology and its participation in atherosclerosis and provokes consideration of the broader existence of local macrophage progenitors in other tissues.
authors.affiliation: From the Division of Cardiovascular Diseases, Mayo Clinic, Rochester, MN (P.J.P., A.S.P., D.B.S., C.D.C., S.J.H., T.A.W., S.D., L.S.K., C.S.M., S.P., R.G., R.D.S.); Monash Cardiovascular Research Centre, Monash University, Clayton, Victoria, Australia (P.J.P.); Department of Medicine, University of Adelaide, Adelaide, South Australia, Australia (P.J.P., S.D.); and Kansas University Medical Center, The University of Kansas, Kansas City (R.D.S).
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Psaltis
authors.affiliation: From the Division of Cardiovascular Diseases, Mayo Clinic, Rochester, MN (P.J.P., A.S.P., D.B.S., C.D.C., S.J.H., T.A.W., S.D., L.S.K., C.S.M., S.P., R.G., R.D.S.); Monash Cardiovascular Research Centre, Monash University, Clayton, Victoria, Australia (P.J.P.); Department of Medicine, University of Adelaide, Adelaide, South Australia, Australia (P.J.P., S.D.); and Kansas University Medical Center, The University of Kansas, Kansas City (R.D.S).
authors.forename: Amrutesh S
authors.initials: AS
authors.lastname: Puranik
authors.affiliation: From the Division of Cardiovascular Diseases, Mayo Clinic, Rochester, MN (P.J.P., A.S.P., D.B.S., C.D.C., S.J.H., T.A.W., S.D., L.S.K., C.S.M., S.P., R.G., R.D.S.); Monash Cardiovascular Research Centre, Monash University, Clayton, Victoria, Australia (P.J.P.); Department of Medicine, University of Adelaide, Adelaide, South Australia, Australia (P.J.P., S.D.); and Kansas University Medical Center, The University of Kansas, Kansas City (R.D.S).
authors.forename: Daniel B
authors.initials: DB
authors.lastname: Spoon
authors.affiliation: From the Division of Cardiovascular Diseases, Mayo Clinic, Rochester, MN (P.J.P., A.S.P., D.B.S., C.D.C., S.J.H., T.A.W., S.D., L.S.K., C.S.M., S.P., R.G., R.D.S.); Monash Cardiovascular Research Centre, Monash University, Clayton, Victoria, Australia (P.J.P.); Department of Medicine, University of Adelaide, Adelaide, South Australia, Australia (P.J.P., S.D.); and Kansas University Medical Center, The University of Kansas, Kansas City (R.D.S).
authors.forename: Colin D
authors.initials: CD
authors.lastname: Chue
authors.affiliation: From the Division of Cardiovascular Diseases, Mayo Clinic, Rochester, MN (P.J.P., A.S.P., D.B.S., C.D.C., S.J.H., T.A.W., S.D., L.S.K., C.S.M., S.P., R.G., R.D.S.); Monash Cardiovascular Research Centre, Monash University, Clayton, Victoria, Australia (P.J.P.); Department of Medicine, University of Adelaide, Adelaide, South Australia, Australia (P.J.P., S.D.); and Kansas University Medical Center, The University of Kansas, Kansas City (R.D.S).
authors.forename: Scott J
authors.initials: SJ
authors.lastname: Hoffman
authors.affiliation: From the Division of Cardiovascular Diseases, Mayo Clinic, Rochester, MN (P.J.P., A.S.P., D.B.S., C.D.C., S.J.H., T.A.W., S.D., L.S.K., C.S.M., S.P., R.G., R.D.S.); Monash Cardiovascular Research Centre, Monash University, Clayton, Victoria, Australia (P.J.P.); Department of Medicine, University of Adelaide, Adelaide, South Australia, Australia (P.J.P., S.D.); and Kansas University Medical Center, The University of Kansas, Kansas City (R.D.S).
authors.forename: Tyra A
authors.initials: TA
authors.lastname: Witt
authors.affiliation: From the Division of Cardiovascular Diseases, Mayo Clinic, Rochester, MN (P.J.P., A.S.P., D.B.S., C.D.C., S.J.H., T.A.W., S.D., L.S.K., C.S.M., S.P., R.G., R.D.S.); Monash Cardiovascular Research Centre, Monash University, Clayton, Victoria, Australia (P.J.P.); Department of Medicine, University of Adelaide, Adelaide, South Australia, Australia (P.J.P., S.D.); and Kansas University Medical Center, The University of Kansas, Kansas City (R.D.S).
authors.forename: Sinny
authors.initials: S
authors.lastname: Delacroix
authors.affiliation: From the Division of Cardiovascular Diseases, Mayo Clinic, Rochester, MN (P.J.P., A.S.P., D.B.S., C.D.C., S.J.H., T.A.W., S.D., L.S.K., C.S.M., S.P., R.G., R.D.S.); Monash Cardiovascular Research Centre, Monash University, Clayton, Victoria, Australia (P.J.P.); Department of Medicine, University of Adelaide, Adelaide, South Australia, Australia (P.J.P., S.D.); and Kansas University Medical Center, The University of Kansas, Kansas City (R.D.S).
authors.forename: Laurel S
authors.initials: LS
authors.lastname: Kleppe
authors.affiliation: From the Division of Cardiovascular Diseases, Mayo Clinic, Rochester, MN (P.J.P., A.S.P., D.B.S., C.D.C., S.J.H., T.A.W., S.D., L.S.K., C.S.M., S.P., R.G., R.D.S.); Monash Cardiovascular Research Centre, Monash University, Clayton, Victoria, Australia (P.J.P.); Department of Medicine, University of Adelaide, Adelaide, South Australia, Australia (P.J.P., S.D.); and Kansas University Medical Center, The University of Kansas, Kansas City (R.D.S).
authors.forename: Cheryl S
authors.initials: CS
authors.lastname: Mueske
authors.affiliation: From the Division of Cardiovascular Diseases, Mayo Clinic, Rochester, MN (P.J.P., A.S.P., D.B.S., C.D.C., S.J.H., T.A.W., S.D., L.S.K., C.S.M., S.P., R.G., R.D.S.); Monash Cardiovascular Research Centre, Monash University, Clayton, Victoria, Australia (P.J.P.); Department of Medicine, University of Adelaide, Adelaide, South Australia, Australia (P.J.P., S.D.); and Kansas University Medical Center, The University of Kansas, Kansas City (R.D.S).
authors.forename: Shuchong
authors.initials: S
authors.lastname: Pan
authors.affiliation: From the Division of Cardiovascular Diseases, Mayo Clinic, Rochester, MN (P.J.P., A.S.P., D.B.S., C.D.C., S.J.H., T.A.W., S.D., L.S.K., C.S.M., S.P., R.G., R.D.S.); Monash Cardiovascular Research Centre, Monash University, Clayton, Victoria, Australia (P.J.P.); Department of Medicine, University of Adelaide, Adelaide, South Australia, Australia (P.J.P., S.D.); and Kansas University Medical Center, The University of Kansas, Kansas City (R.D.S).
authors.forename: Rajiv
authors.initials: R
authors.lastname: Gulati
authors.affiliation: From the Division of Cardiovascular Diseases, Mayo Clinic, Rochester, MN (P.J.P., A.S.P., D.B.S., C.D.C., S.J.H., T.A.W., S.D., L.S.K., C.S.M., S.P., R.G., R.D.S.); Monash Cardiovascular Research Centre, Monash University, Clayton, Victoria, Australia (P.J.P.); Department of Medicine, University of Adelaide, Adelaide, South Australia, Australia (P.J.P., S.D.); and Kansas University Medical Center, The University of Kansas, Kansas City (R.D.S). rsimari@kumc.edu.
authors.forename: Robert D
authors.initials: RD
authors.lastname: Simari
mesh_terms: D019264:Adoptive Transfer; D063194:Adventitia / Q000166:cytology* / Q000276:immunology; D000818:Animals; D000950:Antigens, Ly / Q000378:metabolism; D001011:Aorta / Q000166:cytology / Q000276:immunology; D001057:Apolipoproteins E / Q000235:genetics; D050197:Atherosclerosis / Q000276:immunology / Q000473:pathology*; D002460:Cell Line / Q000276:immunology*; D005260:Female; D006949:Hyperlipidemias / Q000276:immunology / Q000473:pathology; D016130:Immunophenotyping; D017493:Leukocyte Common Antigens / Q000378:metabolism; D008264:Macrophages / Q000166:cytology* / Q000378:metabolism / Q000637:transplantation; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011973:Receptors, LDL / Q000235:genetics; D013154:Spleen / Q000166:cytology; D013234:Stem Cells / Q000166:cytology* / Q000276:immunology
chemical_list: D000950:Antigens, Ly; D001057:Apolipoproteins E; C074650:Ly6a protein, mouse; D008565:Membrane Proteins; D011973:Receptors, LDL; D017493:Leukocyte Common Antigens; C516770:Ptprc protein, mouse
keywords: atherosclerosis; cells; leukocytes; macrophages; monocyte–macrophage precursor cells; progenitor cells