Peter J Psaltis1, Amrutesh S Puranik1, Daniel B Spoon1, Colin D Chue1, Scott J Hoffman1, Tyra A Witt1, Sinny Delacroix1, Laurel S Kleppe1, Cheryl S Mueske1, Shuchong Pan1, Rajiv Gulati1, Robert D Simari2. 1. 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). 2. 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.
Abstract
RATIONALE: 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. METHODS AND 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.
RATIONALE: 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. METHODS AND 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: Marvin E Morris; Jason E Beare; Robert M Reed; Jacob R Dale; Amanda J LeBlanc; Christina L Kaufman; Huaiyu Zheng; Chin K Ng; Stuart K Williams; James B Hoying Journal: Stem Cells Transl Med Date: 2015-02-26 Impact factor: 6.940
Authors: Mark W Majesky; Henrick Horita; Allison Ostriker; Sizhao Lu; Jenna N Regan; Ashim Bagchi; Xiu Rong Dong; Joanna Poczobutt; Raphael A Nemenoff; Mary C M Weiser-Evans Journal: Circ Res Date: 2016-11-09 Impact factor: 17.367