Definitive proof for direct reprogramming of hematopoietic cells to pluripotency
Definitive proof for direct reprogramming of hematopoietic cells to pluripotency
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DOI：
10.1182/blood-2009-02-203695
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发表时间：
2009-08-27
期刊：
影响因子：
20.3
通讯作者：
Nakauchi, Hiromitsu
中科院分区：
文献类型：
--
作者：
Okabe, Motohito;Otsu, Makoto;Nakauchi, Hiromitsu
诱导多能干细胞(IPSCs)的生成通常使用成纤维细胞，但其他细胞来源可能在研究和临床环境中都有用。尽管细胞起源的证明需要目标细胞和已建立的IPSCs中的遗传标记识别，但成熟淋巴细胞以外的体细胞大多缺乏这样的标记。在这里，我们展示了没有重排基因的小鼠造血细胞直接重编程的确凿证据。通过IPSC因子转导，我们成功地从一只小鼠的骨髓祖细胞中获得了IPSCs，该小鼠的造血重建是由单一的同源造血干细胞重建的。已建立的克隆被证明在基因上与移植的单个造血干细胞相同，从而证明了它们的细胞来源。这些来自造血细胞的IPSCs表现出IPSCs的典型特征，包括促进小鼠嵌合体的能力。这些结果将促使进一步使用造血细胞生成IPSC，同时使最终研究能够测试细胞来源如何影响后代IPSCs的特征。(血。2009；114：1764-1767)
Generation of induced pluripotent stem cells (iPSCs) generally uses fibroblastic cells, but other cell sources may prove useful in both research and clinical settings. Although proof of cellular origin requires genetic-marker identification in both target cells and established iPSCs, somatic cells other than mature lymphocytes mostly lack such markers. Here we show definitive proof of direct reprogramming of murine hematopoietic cells with no rearranged genes. Using iPSC factor transduction, we successfully derived iPSCs from bone marrow progenitor cells obtained from a mouse whose hematopoiesis was reconstituted from a single congenic hematopoietic stem cell. Established clones were demonstrated to be genetically identical to the transplanted single hematopoietic stem cell, thus proving their cellular origin. These hematopoietic cell-derived iPSCs showed typical characteristics of iPSCs, including the ability to contribute to chimerism in mice. These results will prompt further use of hematopoietic cells for iPSC generation while enabling definitive studies to test how cellular sources influence characteristics of descendant iPSCs. (Blood. 2009; 114:1764-1767)