Cantas Alev

Research Overview

The Alev lab at the Institute for the Advanced Study of Human Biology (ASHBi), Kyoto University, is interested in and working on the in vitro reconstitution and analysis of human and non-human amniote embryonic development. Our lab focuses foremost on the in vitro recapitulation of mesodermal organogenesis and the reconstitution of complex mesoderm-driven morphogenetic processes. We have recently established an in vitro model of the human segmentation clock and continue to work on the in vitro recapitulation of human and non-human somitogenesis. We are furthermore interested in endodermal and ectodermal organogenesis and complex tissue formation from human and non-human pluripotent stem cells. In collaboration with other scientists at ASHBi our lab aims to establish novel scientific concepts and disruptive technologies in the field of in vitro organogenesis and synthetic embryology, with the overall goal to increase our still limited understanding of human development, evolution and disease.

Fig 1: In vitro reconstitution of the human segmentation clock in health and disease

Publications

Matsuda M, Yamanaka Y, Uemura M, Osawa M, Saito MK, Nagahashi A, Nishio M, Guo L, Ikegawa S, Sakurai S, Kihara S, Maurissen TL, Nakamura M, Matsumoto T, Yoshitomi H, Ikeya M, Kawakami N, Yamamoto T, Woltjen K, Ebisuya M, Toguchida J, Alev C. Recapitulating the human segmentation clock with pluripotent stem cells. Nature. 2020 Apr;580(7801):124-129. https://doi.org/10.1038/s41586-020-2144-9

Matsuda M, Hayashi H, Garcia-Ojalvo J, Yoshioka-Kobayashi K, Kageyama R,Yamanaka Y, Ikeya M, Toguchida J, Alev C, Ebisuya M. Species-specific segmentation clock periods are due to differential biochemical reaction speeds. Science. 2020 Sep 18;369(6510):1450-1455. https://doi.org/10.1126/science.aba7668

Kishimoto K, Furukawa KT, Luz-Madrigal A, Yamaoka A, Matsuoka C, Habu M, Alev C, Zorn AM, Morimoto M. Bidirectional Wnt signaling between endoderm and mesoderm confers tracheal identity in mouse and human cells. Nature Communications. 2020 Aug 27;11(1):4159. https://doi.org/10.1038/s41467-020-17969-w

Hamidi S, Nakaya Y, Nagai H, Alev C, Kasukawa T, Chhabra S, Lee R, Niwa H, Warmflash A, Shibata T, Sheng G. Mesenchymal-epithelial transition regulates initiation of pluripotency exit before gastrulation. Development. 2020 Feb 3;147(3):dev184960. https://doi.org/10.1242/dev.184960

Kawai S, Yoshitomi H, Sunaga J, Alev C, Nagata S, Nishio M, Hada M, Koyama Y, Uemura M, Sekiguchi K, Maekawa H, Ikeya M, Tamaki S, Jin Y, Harada Y, Fukiage K, Adachi T, Matsuda S, Toguchida J. In vitro bone-like nodules generated from patient-derived iPSCs recapitulate pathological bone phenotypes. Nature Biomedical Engineering. 2019 Jul;3(7):558-570. https://doi.org/10.1038/s41551-019-0410-7

McIntyre BA, Alev C, Mechael R, Wu Y, Sheng G, Bhatia M et al. Expansive generation of functional airway epithelium from human embryonic stem cells. Stem Cells Translational Medicine. 2014 Jan; 3(1):7-17. https://doi.org/10.5966/sctm.2013-0119

Alev C, Nakano M, Wu Y, Horiuchi H, Sheng G. Manipulating the avian epiblast and epiblast-derived stem cells. Methods in Molecular Biology. 2013;1074:151-73. https://doi.org/10.1007/978-1-62703-628-3_12

Alev C, Wu Y, Nakaya Y, Sheng G. Decoupling of amniote gastrulation and streak formation reveals a morphogenetic unity in vertebrate mesoderm induction. Development. 2013 Jul;140(13):2691-6. https://doi.org/10.1242/dev.094318

Alev C, Wu Y, Kasukawa T, Jakt LM, Ueda HR, Sheng G. Transcriptomic landscape of the primitive streak. Development. 2010 Sep 1;137(17):2863-74. https://doi.org/10.1242/dev.053462