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The Adhesion Molecule Esam1 Is a Novel Hematopoietic Stem Cell Marker§

机译:粘附分子Esam1是一种新型的造血干细胞标记物 §

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Hematopoietic stem cells (HSCs) have been highly enriched using combinations of 12-14 surface markers. Genes specifically expressed by HSCs as compared with other multipotent progenitors may yield new stem cell enrichment markers, as well as elucidate self-renewal and differentiation mechanisms. We previously reported that multiple cell surface molecules are enriched on mouse HSCs compared with more differentiated progeny. Here, we present a definitive expression profile of the cell adhesion molecule endothelial cell-selective adhesion molecule (Esam1) in hematopoietic cells using reverse transcription-quantitative polymerase chain reaction and flow cytometry studies. We found Esam1 to be highly and selectively expressed by HSCs from mouse bone marrow (BM). Esam1 was also a viable positive HSC marker in fetal, young, and aged mice, as well as in mice of several different strains. In addition, we found robust levels of Esam1 transcripts in purified human HSCs. Esam1-/- mice do not exhibit severe hematopoietic defects; however, Esam1-/- BM has a greater frequency of HSCs and fewer T cells. HSCs from Esam1-/- mice give rise to more granulocyte/monocytes in culture and a higher T cell:B cell ratio upon transplantation into congenic mice. These studies identify Esam1 as a novel, widely applicable HSC-selective marker and suggest that Esam1 may play roles in both HSC proliferation and lineage decisions. STEM CELLS 2009;27:653-661
机译:造血干细胞(HSC)已使用12-14个表面标记的组合高度富集。与其他多能祖细胞相比,HSCs特异表达的基因可能会产生新的干细胞富集标记,并阐明自我更新和分化机制。我们以前曾报道过,与更分化的后代相比,小鼠HSC上富含多种细胞表面分子。在这里,我们使用逆转录-定量聚合酶链反应和流式细胞术研究在造血细胞中的细胞粘附分子内皮细胞选择性粘附分子(Esam1)的明确表达谱。我们发现Esam1是由小鼠骨髓(BM)的HSC高度选择性表达的。 Esam1在胎儿,年轻和老年小鼠以及几种不同品系的小鼠中也是可行的HSC阳性标记。此外,我们在纯化的人类HSCs中发现了强大的Esam1转录本水平。 Esam1-/-小鼠没有表现出严重的造血缺陷。然而,Esam1-/-BM的HSC频率更高,而T细胞更少。来自Esam1-/-小鼠的HSC在移植到同基因小鼠中后,会在培养物中产生更多的粒细胞/单核细胞,并产生更高的T细胞:B细胞比率。这些研究将Esam1确定为一种新颖的,可广泛应用的HSC选择标记,并表明Esam1可能在HSC增殖和谱系决定中发挥作用。干细胞2009; 27:653-661

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    《STEM CELLS》 |2009年第3期|653-661|共9页
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    Institute of Stem Cell Biology and Regenerative Medicine, Departments of Pathology, Chemical and Systems Biology and Developmental Biology, Falk Cardiovascular Research Building, Stanford University School of Medicine, Stanford, California, USA;

    Institute of Stem Cell Biology and Regenerative Medicine, Departments of Pathology, Chemical and Systems Biology and Developmental Biology, Falk Cardiovascular Research Building, Stanford University School of Medicine, Stanford, California, USA;

    Institute of Stem Cell Biology and Regenerative Medicine, Departments of Pathology, Chemical and Systems Biology and Developmental Biology, Falk Cardiovascular Research Building, Stanford University School of Medicine, Stanford, California, USA;

    Department of Vascular Cell Biology, Max-Planck Institute for Molecular Biomedicine, Münster, Germany;

    Department of Vascular Cell Biology, Max-Planck Institute for Molecular Biomedicine, Münster, Germany;

    Division of Cardiovascular Medicine, Falk Cardiovascular Research Building, Stanford University School of Medicine, Stanford, California, USA;

    Division of Cardiovascular Medicine, Falk Cardiovascular Research Building, Stanford University School of Medicine, Stanford, California, USA;

    Institute of Stem Cell Biology and Regenerative Medicine, Departments of Pathology, Chemical and Systems Biology and Developmental Biology, Falk Cardiovascular Research Building, Stanford University School of Medicine, Stanford, California, USA;

    Institute for Biology of Stem Cells, Department of Biomolecular Engineering, University of California Santa Cruz, Santa Cruz, California, USA;

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