Submitted February 5, 2009
Accepted May 11, 2009
Definitive proof for direct reprogramming of hematopoietic cells to pluripotency
Motohito Okabe, Makoto Otsu, Dong Hyuck Ahn, Toshihiro Kobayashi, Yohei Morita, Yukiko Wakiyama, Masafumi Onodera, Koji Eto, Hideo Ema, and Hiromitsu Nakauchi*
Division of Stem Cell Therapy, Center for Stem Cell and Regenerative Medicine, Institute of Medical Science, University of Tokyo, Tokyo, Japan
Japan Science Technology Agency, ERATO, Nakauchi Stem Cell and Organ Regeneration Project, Tokyo, Japan
Department of Genetics, National Research Institute for Child Health and Development, Tokyo, Japan
* Corresponding author; email: nakauchi{at}ims.u-tokyo.ac.jp.
Generation of induced pluripotent stem cells (iPSCs) generally utilizes 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 (HSC). Established clones were demonstrated to be genetically identical to the transplanted single HSC, thus proving their cellular origin. These hematopoietic cell-derived iPSCs showed typical characteristics of iPSCs, including 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.
