Laboratory for Pluripotent Stem Cell Studies

Pluripotent stem cells such as embryonic stem (ES) cells have an ability to differentiate into all cell types found in an organism. ES cells continue to unlimitedly propagate via self-renewal with keeping pluripotency in the optimal culture condition. How is pluripotency is established and maintained in molecular level? We have revealed the role of the soluble factors including LIF (leukemia inhibitory factor), Nodal and Wnt as well as the functions of the pluripotent cell-specific transcription factors such as Oct3/4, Sox2 and Nanog. Now we are trying to reveal how the regulations of cell-cycle, cytoskeletal organization and epigenetic states involve in the molecular mechanism to maintain pluripotency under the controll of the transcription factors.

Research Subjects

• Molecular mechanisms to establish and maintain pluripotency

Publications

1. Masui, S., Shimosato, D., Toyooka, Y., Yagi, R., Takahashi, K. and Niwa, H.:
   "An efficient system to establish multiple embryonic stem cell lines carrying an inducible expression unit"
   Nucleic Acids Res., 33, e43, 2005
2. Niwa, H., Toyooka, Y., Shimosato, D., Strumpf, D., Takahashi, K., Yagi, R. and Rossant, J.:
   "Interaction between Oct3/4 and Cdx2 determines trophectoderm differentiation"
   Cell, 123, 917-929, 2005
3. Nakatake, Y., Fukui, N., Iwamatsu, Y., Masui, S., Takahashi, K., Yagi, R., Yagi, K., Miyazaki, J.-I., Matoba, R., Ko, M.S.H. and Niwa, H.:
   "Klf4 cooperates with Oct3/4 and Sox2 to activate the Lefty1 core promoter in embryonic stem cells"
   Mol. Cell. Biol., 26, 7772-7782, 2006
4. Ogawa, K., Saito, A., Matui, H., Suzuki, H., Ohtsuka, S, Shimosato, D., Morishita, Y., Watabe, T., Niwa, H. and Miyazono, K.:
   "Activin/Nodal signaling is involved in propagation of mouse embryonic stem cells"
   J. Cell Sci., 120, 55-65, 2007
5. Niwa, H.:
   "How is pluripotency determined and maintained"
   Development, 134, 635-646, 2007
6. Masui, S., Nakatake, Y., Toyooka, Y., Shimosato, D., Yagi, R., Takahashi, K., Okochi, H., Okuda, A., Matoba, R., Sharov, A., Ko, M.S.H. and Niwa, H.:
   "Pluripotency governed by Sox2 via regulation of Oct3/4 expression in mouse embryonic stem cells"
   Nat. Cell. Biol., 9, 625-635, 2007
7. Shimosato, D., Shiki, M. and Niwa, H.:
   "Extra-embryonic endoderm cells derived from ES cells induced by GATA factors acquire the character of XEN cells"
   BMC Dev. Biol.,7, 80, 2007
8. Toyooka, Y., Shimosato, D., Murakami, K. and Niwa, H.:
   "Identification and characterization of subpopulations in undifferentiated ES cell culture"
   Development, 135, 909-918, 2008
9. Niwa, H.*, Ogawa, K., Shimosato, D. and Adachi, K.:
   "A parallel circuit of LIF signaling pathways maintains pluripotency of mouse ES cells. "
   Nature, 460, 118-122, 2009
10. Murakami, K., Araki, K., Ohtsuka, S., Wakayama, T. and Niwa, H.*:
    "Choice of random rather than imprinted X inactivation in female ES cell-derived extra-embryonic cells. "
    Development,138, 197-202, 2011