Identification of a monocyte-predisposed hierarchy of hematopoietic progenitor cells in the adventitia of postnatal murine aorta.
Identification of a monocyte-predisposed hierarchy of hematopoietic progenitor cells in the adventitia of postnatal murine aorta.
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DOI：
10.1161/circulationaha.111.059360
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发表时间：
2012-01-31
期刊：
影响因子：
37.8
通讯作者：
Simari RD
中科院分区：
文献类型：
--
作者：
Psaltis PJ;Harbuzariu A;Delacroix S;Witt TA;Holroyd EW;Spoon DB;Hoffman SJ;Pan S;Kleppe LS;Mueske CS;Gulati R;Sandhu GS;Simari RD
在胚胎发育过程中，造血起源于背主动脉。虽然成人血管含有内皮细胞和平滑肌细胞的祖细胞，但尚不清楚它们是否含有造血祖细胞(HPC)或干细胞(HSCs)。这里，我们假设动脉壁是出生后生活中HPC和HSCs的来源。取成年饲喂C57BL/6和载脂蛋白E的−/−小鼠，制备单细胞主动脉解聚体。在短期和长期以甲基纤维素为基础的培养中，主动脉细胞产生了广泛的多能和谱系特异性的造血祖细胞集落形成单位(CFU)，其中以巨噬细胞CFU-M为主。这种克隆形成能力在无病变的载脂蛋白E−/−小鼠中较高，并且主要定位于外膜中的Sca-1+细胞。SCA-1在主动脉中的表达与典型的HSC标志物以及CD45和成熟白细胞抗原共同定位。将标记的GFP转基因供者的主动脉细胞过继转移到照射后的C57BL/6受体，证实了稀有HSCs的含量(每400万个细胞中有1个)，能够自我更新和持久的、低水平的白细胞重建。此外，受者骨髓和脾中仅有CFU-M的GFP+集落恢复较晚，表明长期巨噬细胞前体占优势。虽然骨髓运输被证明在辐射后补充了一些主动脉的造血潜能，但大多数巨噬细胞前体似乎是在局部出现的，这表明长期滞留在血管壁。出生后的小鼠主动脉含有罕见的多潜能HPC/HSCs，并选择性地富含SCA-1+单核/巨噬细胞前体。这些人群可能代表了炎性细胞的新的局部血管来源。
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. 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. 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.