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 - Reprogramming Science - Center for iPS Cell Research and Application (CiRA)
Laboratory of Reprogramming Regulation
The generation of induced Pluripotent Stem (iPS) cells with four defined transcription factors has led to the expectation that we will be able to better understand various pathologies, and discover new drugs by using cells obtained from patients, and thereby be able to carry out successful medical transplantation. However, before this new treatment modality can be clinically applied, strict evaluations must be performed while always maintaining patient safety as the first priority. To this end, we have tried to identify the optimal reprogramming factors, while continually improving the methods for iPS cell generation, and also establish effective evaluation methods to ensure the safety of iPS cells. At the same time, we have also focused our attention on the molecular mechanisms underlying the reprogramming process. At the end of the day, we would like to positively contribute to the achievement of successful regenerative medicine utilizing pluripotent stem cells based on the steady accumulation of knowledge in this important field of study.

  Shinya Yamanaka M.D., Ph.D.
Research and Education
We previously were able to successfully transform fibroblasts into a pluripotent state using a set of four defined transcription factors (Oct3/4, Sox2, Klf4 and c-Myc) by means of retroviral transduction. These artificially established cells have both potentials and characteristics similar to those of embryonic stem (ES) cells, and thus are called induced Pluripotent Stem (iPS) cells. Because human iPS cells are expected to become useful tools for both better understanding various pathologies, as well as for the discovery of new drugs, this technology has thus been rapidly evolving. In addition, iPS cells are also a potentially useful source for cell transplantation without any danger of immunological rejection. We have conducted numerous analyses to improve the quality of iPS cells. According to previous results, we have identified several issues regarding iPS cells which still have to be overcome before they can be used for clinical application. We believe that it is important to understand the molecular mechanisms underlying the reprogramming process and the network of pluripotency for the achievement of our ultimate goal, namely the generation of clinical-grade iPS cells. Our field consists of seven groups, and each of them has a unique standpoint and background. By utilizing fusion, molecular and cellular biology techniques and bioinformatics, we have been continually evaluating the bottom line of reprogramming and pluripotency from various perspectives. At the end of the day, our results are expected to positively contribute to the identification of the best sources and methods for iPS cell generation, while also establishing stable culture conditions for effective clinical application.

Reprogramming Science,
Center for iPS Cell
Research and Application (CiRA)
Laboratory of Reprogramming Regulation
Professor Shinya Yamanaka
TEL 075-366-7044
FAX 075-366-7042
Recent Publications
1. Maekawa, M., Yamaguchi, K., Nakamura, T., Shibukawa, R., Kodanaka, I., Ichisaka, T., Kawamura, Y., Mochizuki, H., Goshima, N., and Yamanaka, S. Direct reprogramming of somatic cells is promoted by maternal transcription factor Glis1. Nature 474(7350):225-229, 2011.
2. Okita, K., Matsumura, Y., Sato, Y., Okada, A., Morizane, A., Okamoto, S., Hong, H., Nakagawa, M., Tanabe, K., Tezuka, K., Shibata, T., Kunisada, T., Takahashi, M., Takahashi, J., Saji, H., and Yamanaka, S. A more efficient method to generate integration-free human iPS cells. Nat Methods 8(5):409-412, 2011.
3. Nakagawa, M., Takizawa, N., Narita, M., Ichisaka, T., and Yamanaka, S. Promotion of direct reprogramming by transformation-deficient Myc. Proc Natl Acad Sci U S A. 107(32):14152-14157, 2010.
4. Yoshida, Y., Takahashi, K, Okita, K., Ichisaka, T., and Yamanaka, S. Hypoxia Enhances the Generation of Induced Pluripotent Stem Cells. Cell Stem Cell 5:237-241, 2009.
5. Hong, H., Takahashi, K., Ichisaka, T., Aoi, T., Kanagawa, O., Nakagawa, M., Okita, K., and Yamanaka, S. Suppression of induced pluripotent stem cell generation by the p53–p21 pathway. Nature 460: 1132-1135, 2009.
Human iPS cells generated with L-Myc (upper photo). Germline transmission of mouse L-Myc iPS cells (lower photo).
Human iPS cells derived from adult human dermal fibroblasts.
Cartilage derived from iPS cells putatively homozygous for the HLA-A, B, and DRB1 loci.
Laboratory members