An in vivo analysis of hematopoietic stem cell potential - Hematopoietic origin of cardiac valve interstitial cells
An in vivo analysis of hematopoietic stem cell potential - Hematopoietic origin of cardiac valve interstitial cells
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DOI：
10.1161/01.res.0000207384.81818.d4
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发表时间：
2006-03-17
影响因子：
20.1
通讯作者：
Drake, CJ
中科院分区：
文献类型：
--
作者：
Visconti, RP;Ebihara, Y;Drake, CJ
最近评估造血干细胞 (HSC) 潜力的研究提出了这样一种可能性：除了胚胎来源之外，成体瓣膜成纤维细胞也可能源自 HSC。为了检验这一假设，我们使用了可在体内评估单个 HSC 潜力的方法。这是通过从普遍表达增强型绿色荧光蛋白（EGFP）的小鼠骨髓中分离和克隆扩增单谱系阴性（Lin（-））、c-kit（+）、Sca-1（+）、CD34（-）细胞，并将源自这些候选HSC的单个克隆群移植到经致死辐射的同源非EGFP小鼠中来实现的。对克隆移植受体小鼠瓣膜组织的组织学分析表明，宿主瓣膜内存在大量 EGFP(+) 细胞。这些细胞的一个亚群表现出成纤维细胞的合成特性，其前胶原 1 α 1 mRNA 的表达证明了这一点。此外，通过雌雄移植小鼠的 Y 染色体特异性荧光原位杂交分析表明，EGFP(+) 瓣膜细胞是 HSC 衍生细胞分化的结果，而不是 EGFP(+) 供体细胞与宿主体细胞融合的结果。总之，这些发现证明了 HSC 对成人瓣膜成纤维细胞群的贡献。
Recent studies evaluating hematopoietic stem cell (HSC) potential raise the possibility that, in addition to embryonic sources, adult valve fibroblasts may be derived from HSCs. To test this hypothesis, we used methods that allow the potential of a single HSC to be evaluated in vivo. This was achieved by isolation and clonal expansion of single lineage-negative (Lin(-)), c-kit(+), Sca-1(+), CD34(-) cells from the bone marrow of mice that ubiquitously express enhanced green fluorescent protein (EGFP) combined with transplantation of individual clonal populations derived from these candidate HSCs into a lethally irradiated congenic non-EGFP mouse. Histological analyses of valve tissue from clonally engrafted recipient mice revealed the presence of numerous EGFP(+) cells within host valves. A subpopulation of these cells exhibited synthetic properties characteristic of fibroblasts, as evidenced by their expression of mRNA for procollagen 1 alpha 1. Further, we show by Y-chromosome-specific fluorescence in situ hybridization analysis of female-to-male transplanted mice that the EGFP(+) valve cells are the result of HSC-derived cell differentiation and not the fusion of EGFP(+) donor cells with host somatic cells. Together, these findings demonstrate HSC contribution to the adult valve fibroblast population.