Kenta Yashiro moved from Japan to WHRI as a lecturer in Translational Medicine and Therapeutics in September 2007 and had been promoted to be a senior lecturer since July 2010. He graduated Osaka University Medical School in Japan in 1993, and once worked as a paediatrician/neonatologists. Such experience made him interested in developmental biology, and he took PhD course in the lab facilitated by Professor Hiroshi Hamada, an internationally-recognized scientist. He obtained his PhD at Osaka University (1996-2000), completed post-doctoral fellowships at the same lab (2000-2005) and was promoted to be an assistant professor (2000-2007). In his lab, he had been engaged in the study of left-right asymmetry of the vertebrates (Nature 450, 285-288 (2007) etc.) as well as of the effect retinoic acid on the embryogenesis (Developmental Cell 11, 495-504 (2006) etc.).
Currently, his main interest is focused on the molecular mechanism of how cardiac progenitor cells acquire their identity in the early embryos. This knowledge must be useful for the development of a new therapy to regenerate the failed heart.
Summary of Research
Cardiac Stem Cell Science
Despite the current advances in medicine, heart failure remains a major cause of morbidity and mortality in industrialized countries. Therefore the development of new therapeutic approaches is needed. Myocardial regenerative therapy is a promising strategy. However, our knowledge, particularly on the mechanism underlying cardiomyogenic differentiation is still insufficient for this emerging approach to be established. We believe that, for this ultimate purpose, it is now important to further accumulate basic science knowledge of cardiomyogenic differentiation by studying the differentiation of cardiac progenitor cells to cardiomyocytes. For this purpose, we are now mainly promoting the following research projects:
The study of the expression profile of cardiac progenitor cells with deep sequencing of single cell cDNAs.
- To search a novel specific surface marker.
- To comprehend the transcription factors specifically expressed, which must be useful for direct reprogramming of somatic cells to cardiomyocytes.
- To understanding the ongoing signal pathway in the early cardiac progenitor cells.
The study of Tbx5-expressing cardiac progenitor cells, which is the origin of the left ventricle and the atrium.
- Multipotent or not.
- Tracing the progenies in vivo.
The study of the cell fate determination of cardiac progenitor cells to the endocardium.
Figure 1. Cardiac progenitor cells in mouse embryo of embryonic day 7
Section of an embryonic day 7 mouse embryo was stained with anti-Nkx2-5 antibody (red color) and anti-Sox17andibody (green color), labeling cardiac progenitor cells and endoderm cells, respectively. Nuclei were stained with DAPI as blue. White arrows indicate Nkx2-5-positive cardiac progenitor cells, which we are studying. Scale bar indicates 50 μm.
T-box transcription factor Tbx5 is responsible for Holt-Oram syndrome, which plays its important role in the development of the heart and the limb. To trace Tbx5-expressing cells, we constructed the transgene whose Tbx5 genomic allele derived from bacterial artificial chromosome (BAC) was knocked-in by CreERT2 cassette. This transgene enables us to trace the progenitor cells which will compose the future heart (red arrow) and limb (black arrow).
For a full list of publist publications click here
A simple and novel method for RNA-seq library preparation of single cell cDNA analysis by hyperactive Tn5 Transposase Dev Dyn under the first revision (2012). Publications (auto link to QMUL list (TAB)) 1. Brouilette, S.W, Kuersten, S, Mein, C., Bozek, M, Terry, A, Dias, K, Bhaw-Rosun, L, Shintani, Y, Coppen, S.R, Ikebe, C, Sawhney, V, Campbell, N, Kaneko, M, Tano, N, Ishida, H, Suzuki, K. & Yashiro, K.
EpCAM contributes to formation of functional tight junction in the intestinal epithelium by recruiting claudin proteins. Developmental Biology in press (2012). Lei, Z, Maeda, T, Tamura, A, Nakamura, T, Yamazaki, Y, Shiratori, H, Yashiro, K., Tsukita, S. & Hamada, H.
Retinoic acid signaling regulates Sonic hedgehog and bone morphogenetic protein signalings during genital tubercle development. Birth Defects Res B Dev Reprod Toxicol (2011). Liu, L, Suzuki, K, Nakagata, N, Mihara, K, Matsumaru, D, Ogino, Y, Yashiro, K, Hamada, H, Liu, Z, Evans, S.M, Mendelsohn, C. & Yamada, G.
Left-right asymmetry in the level of active Nodal protein produced in the node is translated into left-right asymmetry in the lateral plate of mouse embryos. Kawasumi, A. Developmental Biology 353, 321-330 (2011). Nakamura, T, Iwai, N, Yashiro, K, Saijoh, Y, Belo, J.A, Shiratori, H. & Hamada, H.
Removal of maternal retinoic acid by embryonic CYP26 is required for correct Nodal expression during early embryonic patterning. Genes Dev 23, 1689-1698 (2009). Uehara, M, Yashiro, K, Takaoka, K, Yamamoto, M. & Hamada, H.
Donor cell-type specific paracrine effects of cell transplantation for post-infarction heart failure. J Mol Cell Cardiol 47, 288-295 (2009).Shintani, Y, Fukushima, S, Varela-Carver, A, Lee, J, Coppen, S.R., Takahashi, K, Brouilette, S.W, Yashiro, K, Terracciano, C.M, Yacoub, M.H. & Suzuki, K.
Modulated inflammation by injection of high-mobility group box 1 recovers post-infarction chronically failing heart. Circulation 118, S106-114 (2008). Takahashi, K, Fukushima, S, Yamahara, K, Yashiro, K, Shintani, Y, Coppen, S.R, Salem, H.K, Brouilette, S.W, Yacoub, M.H. & Suzuki, K.
A factor underlying late-phase arrhythmogenicity after cell therapy to the heart: global downregulation of connexin43 in the host myocardium after skeletal myoblast transplantation. Circulation 118, S138-144 (2008). Coppen, S.R, Fukushima, S, Shintani, Y, Takahashi, K, Varela-Carver, A, Salem, H, Yashiro, K, Yacoub, M.H. & Suzuki, K.
Haemodynamics determined by a genetic programme govern asymmetric development of the aortic arch. Nature 450, 285-288 (2007). Yashiro, K, Shiratori, H. & Hamada, H.
CYP26A1 and CYP26C1 cooperatively regulate anterior-posterior patterning of the developing brain and the production of migratory cranial neural crest cells in the mouse. Developmental Biology 302, 399-411 (2007). Uehara, M, Yashiro, K, Mamiya, S, Nishino, J, Chambon, P, Dolle, P. & Sakai, Y.
Conserved regulation and role of Pitx2 in situs-specific morphogenesis of visceral organs. Development 133, 3015-3025 (2006). Shiratori, H, Yashiro, K, Shen, M.M. & Hamada, H.
Generation of robust left-right asymmetry in the mouse embryo requires a self-enhancement and lateral-inhibition system. Developmental Cell 11, 495-504 (2006). Nakamura, T, Mine, N, Nakaguchi, E, Mochizuki, A, Yamamoto, M, Yashiro, K, Meno, C. & Hamada, H.
Retinoid signaling determines germ cell fate in mice. Science, 596-600 (2006). Bowles, J., Knight, D, Smith, C, Wilhelm, D, Richman, J, Mamiya, S, Yashiro, K, Chawengsaksophak, K, Wilson, M.J, Rossant, J, Hamada, H. & Koopman, P.
Regulation of retinoic acid distribution is required for proximodistal patterning and outgrowth of the developing mouse limb. Developmental Cell 6, 411-422 (2004). Yashiro, K, Zhao, X, Uehara, M, Yamashita, K, Nishijima, M, Nishino, J, Saijoh, Y, Sakai, Y. & Hamada, H.
Identification of a novel left-right asymmetrically expressed gene in the mouse belonging to the BPI/PLUNC superfamily. Dev Dyn 229, 373-379 (2004). Hou, J., Yashiro, K., Okazaki, Y., Saijoh, Y., Hayashizaki, Y. & Hamada, H.
Role of asymmetric signals in left-right patterning in the mouse. American Journal of Medical Genetics 101, 324-327 (2001). Hamada, H., Meno, C., Saijoh, Y., Adachi, H., Yashiro, K., Sakuma, R. & Shiratori, H.
Distinct transcriptional regulation and phylogenetic divergence of human LEFTY genes. Genes Cells 5, 343-357 (2000).Yashiro, K., Saijoh, Y., Sakuma, R., Tada, M., Tomita, N., Amano, K., Matsuda, Y., Monden, M., Okada, S. & Hamada, H.
Left-right asymmetric expression of lefty2 and nodal is induced by a signaling pathway that includes the transcription factor FAST2. Molecular Cell 5, 35-47 (2000). Saijoh, Y., Adachi, H., Sakuma, R., Yeo, C.Y., Yashiro, K., Watanabe, M., Hashiguchi, H., Mochida, K., Ohishi, S., Kawabata, M., Miyazono, K., Whitman, M. & Hamada, H.
Lefty-1 is required for left-right determination as a regulator of lefty-2 and nodal. Cell 94, 287-297 (1998).Meno, C., Shimono, A., Saijoh, Y., Yashiro, K., Mochida, K., Ohishi, S., Noji, S., Kondoh, H. & Hamada, H.