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 somatic 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. As a new direction, his group recently initiated to investigate how circadian rhythms regulate cell proliferation and differentiation.
Lowe, M … Kikyo, N. Cry2 is critical for circadian regulation of myogenic differentiation by Bclaf1-mediated mRNA stabilization of cyclin D1 and Tmem176b. Cell Rep 22, 2118-2132 (2018).
Lowe, M., Hostager, R. & Kikyo, N. Preservation of epigenetic memory during DNA replication. J Stem Cell Res Ther 1, 00007 (2016).
Robinson, C., Lowe, M., Schwartz, A. & Kikyo, N. Mechanisms and Developmental Roles of Promoter-proximal Pausing of RNA Polymerase II. J Stem Cell Res Ther 6, 330 (2016).
Hirai, H., Firpo, M. & Kikyo, N. Establishment of leukemia inhibitory factor (LIF)-independent iPS cells with potentiated Oct4. Stem Cell Res 15, 469-480 (2015).
Hirai, H. & Kikyo, N. Inhibitors of suppressive histone modification promote direct reprogramming of fibroblasts to cardiomyocyte-like cells. Cardiovasc Res 102, 188-190. (2014).
Hirai, H., Katoku-Kikyo, N., Keirstead, S.A. & Kikyo, N. Accelerated direct reprogramming of fibroblasts into cardiomyocyte-like cells with the MyoD transactivation domain. Cardiovasc Res 100, 105-13. (2013).
Hirai, H., Firpo, M. & Kikyo, N. Establishment of LIF-dependent human iPS cells closely related to basic FGF-dependent authentic iPS cells. PLoS One 7, e39022 (2012).
Hirai, H. … Kikyo, N. Radical acceleration of nuclear reprogramming by chromatin remodeling with the transactivation domain of MyoD. Stem Cells 29, 1349-61, (2011).