The long-term goal of Dr. Kikyo's group is to understand molecular mechanisms underlying pluripotency and cell differentiation. This study is expected to contribute to the development of regenerative medicine. His group has been using somatic cell nuclear cloning in Xenopus and induced pluripotent stem cells (iPSCs) of mouse and human to investigate pluripotency. His group established an in vitro model of Xenopus nuclear cloning by incubating egg extract and somactic cell nuclei. From this study, they identified the SWI/SNF ATPase ISWI, the nucleolar disassembly proteins FRGY2a/b, and the histone chaperon nucleoplasmin as key proteins for nuclear remodeling in nuclear cloning. More recently, his group fused the powerful transactivation domain of MyoD to the pluripotency protein Oct4 and radically improved the efficiency of making iPSCs. In addition, fusion of the same domain to the cardiac transcription factor Mef2c facilitates the reprogramming of fibroblasts to cardiomyocyte-like cells. His group continues the search for other key regulators necessary for the reprogramming of a cell differentiation state.
Selected Publications (Pubmed Search)
Hirai, H., and Kikyo, N. (2014) Inhibitors of suppressive histone modification promote direct reprogramming of fibroblasts to cardiomyocyte-like cells. Cardiovas Res 102, 188-190.
Hirai, H., Katoku-Kikyo, N., Keirstead, S.A. and Kikyo, N. (2013) Accelerated direct reprogramming of fibroblasts into cardiomyocyte-like cells with the MyoD transactivation domain. Cardiovas Res. 100, 105-113.
Hirai, H., Katoku-Kikyo, N., Karian, P., Firpo, M. and Kikyo, N. (2012) Efficient iPS cell production with the MyoD transactivation domain in serum-free culture. PLoS ONE 7, e34149
Hirai, H., Firpo, M., and Kikyo, N. (2012) Establishment of LIF-dependent human iPS cells closely related to basic FGF-dependent authentic iPS cells. PLoS ONE 7, e39022
Hirai, H. Karian, P., and Kikyo, N. (2011) Regulation of embryonic stem cell self-renewal and pluripotency by leukemia inhibitory factor. Biochemical J, 438, 11-23.
Hirai H, Tani T, Katoku-Kikyo N, Kellner S, Karian P, Firpo M, Kikyo N. (2011) Radical Acceleration of Nuclear Reprogramming by Chromatin Remodeling With the Transactivation Domain of MyoD. Stem Cells, 29, 1349-61.
Gonda K, Fowler J, Katoku-Kikyo N, Haroldson J, Wudel J, and Kikyo N. (2003) Reversible disassembly of somatic nucleoli by the germ cell proteins FRGY2a and FRGY2b. Nature Cell Biol 5, 205-10.
Kikyo N., Wade P.A, Guschin D., Ge H., and Wolffe AP. (2000) Active remodeling of somatic nuclei in egg cytoplasm by the nucleosomal ATPase ISWI. Science 289, 2360-2.