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 Blood, 27 August 2009, Vol. 114, No. 9, pp. 1764-1767.
Prepublished online as a Blood First Edition Paper on June 29, 2009; DOI 10.1182/blood-2009-02-203695.

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HEMATOPOIESIS AND STEM CELLS

Brief Report

Definitive proof for direct reprogramming of hematopoietic cells to pluripotency

Motohito Okabe1,*, Makoto Otsu1,*, Dong Hyuck Ahn1, Toshihiro Kobayashi1, Yohei Morita1, Yukiko Wakiyama2, Masafumi Onodera3, Koji Eto1, Hideo Ema1, and Hiromitsu Nakauchi1,2

1 Division of Stem Cell Therapy, Center for Stem Cell and Regenerative Medicine, Institute of Medical Science, University of Tokyo, Tokyo; 2 Japan Science and Technology Agency, Exploratory Research for Advanced Technology, Nakauchi Stem Cell and Organ Regeneration Project, Tokyo; and 3 Department of Genetics, National Research Institute for Child Health and Development, Tokyo, Japan

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.


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