Adult murine bone marrow-derived very small embryonic-like stem cells differentiate into the hematopoietic lineage after coculture over OP9 stromal cells.
Adult murine bone marrow-derived very small embryonic-like stem cells differentiate into the hematopoietic lineage after coculture over OP9 stromal cells.
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DOI：
10.1016/j.exphem.2010.10.007
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发表时间：
2011-02
影响因子：
2.6
通讯作者：
Ratajczak, Mariusz Z.
中科院分区：
文献类型：
--
作者：
Ratajczak, Janina;Wysoczynski, Marcin;Zuba-Surma, Ewa;Wan, Wu;Kucia, Magda;Yoder, Mervin C.;Ratajczak, Mariusz Z.
我们最近在成年小鼠骨髓中发现了一组小的Sca-1+/Lin−/CD45SSEA−细胞，它们表达几种上胚系/生殖系和多能干细胞标记物(如OCT-4和SSEA-4)，我们将其命名为非常小的胚胎样干细胞(VSEL)。在这份报告中，我们测试了VSEL可以沿着血液/淋巴系分化的假设。从BM VSEL中纯化的VSEL在OP9基质细胞系上进行预充/共培养，然后在体外和体内检测其造血活性。在平行实验中，对来自VSEL的细胞进行了造血基因和表面标志的表达评估。虽然我们观察到新鲜分离的VSEL在体外和体内都没有表现出造血潜力，但它们在与OP9基质细胞共培养后，可能会以类似于胚胎干细胞或可诱导的多能干细胞的方式沿着造血系分化。“OP9-Primed，”VSEL来源的细胞获得了几个血液/淋巴系特异性基因和标记的表达，在体外产生了造血系集落，并在移植后的一次和二次移植模型中保护了受到致命性辐射的小鼠。我们还观察到，与造血干细胞(HSCs)相比，VSEL对全身照射具有高度的抵抗力。基于这些观察，我们推测VSEL是最原始的小鼠骨髓干细胞群体，有可能成为特定的造血系，因此可能分享长期重新填充HSCs的一些特征。
We recently identified a population of small Sca-1+/Lin−/CD45− cells in adult murine bone marrow that express several epiblast/germ line and pluripotent stem cell markers (e.g., Oct-4 and SSEA-4) that we named “very small embryonic-like stem cells” (VSELs). In this report, we test the hypothesis that VSELs can differentiate along the hemato/lymphopoietic lineage. Purified from BM VSELs were primed/co-cultured over OP9 stroma cell line and subsequently tested in vitro and in vivo assays for their hematopoietic potential. In parallel cells derived from VSELs were evaluated for expression of hematopoietic genes and surface markers. While we observed that freshly isolated VSELs do not exhibit in vitro and in vivo hematopoietic potential, they may, after co-culture over OP9 stromal cells, differentiate along the hematopoietic lineage in a similar way as embryonic stem cells or inducible pluripotent stem cells. “OP9-primed,” VSEL-derived cells acquired expression of several hemato/lymphopoiesis-specific genes and markers, gave rise to hematopoietic colonies in vitro, and protected lethally irradiated mice in both primary and secondary transplant models upon transplantation. We also observed that, compared to hematopoietic stem/progenitor cells (HSCs), VSELs are highly resistant to total body irradiation. Based on these observations, we postulate that VSELs are the most primitive murine BM-residing population of stem cells that have the potential to become specified into the hematopoietic lineage and thus may share some of the characteristics of long-term repopulating HSCs.
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