@article{a492c31a694c4dc099351e9d22c8c9aa,
title = "Ocular surface ectoderm instigated by WNT inhibition and BMP4",
abstract = "We sought to elucidate how and when the ocular surface ectoderm commits to its differentiation into the corneal epithelium in eye development from human induced pluripotent stem cells (hiPSCs) under the influence of WNT signaling and the actions of BMP4. These signals are key drivers ocular surface ectodermal cell fate determination. It was discovered that secreted frizzled related protein-2 (SFRP2) and Dickkopf1 (DKK1), which are expressed in neural ectoderm, are both influential in the differentiation of hiPSCs, where they act as canonical WNT antagonists. BMP4, moreover, was found to simultaneously initiate non-neural ectodermal differentiation into a corneal epithelial lineage. Combined treatment of hiPSCs with exogenous BMP4 aligned to WNT inhibition for the initial four days of differentiation increased the ocular surface ectodermal cell population and induced a corneal epithelial phenotype. Specification of a surface ectodermal lineage and its fate is thus determined by a fine balance of BMP4 exposure and WNT inhibition in the very earliest stages of human eye development.",
keywords = "BMP4, Corneal epithelium, Epithelial stem cells, Human iPS cells, Ocular surface ectoderm, WNT signaling",
author = "Yuki Kobayashi and Ryuhei Hayashi and Shun Shibata and Quantock, {Andrew J.} and Kohji Nishida",
note = "Funding Information: The authors wish to thank Y. Ishikawa of Osaka University for providing excellent technical support and scientific discussions. This work was supported in part by the Project for the Realization of Regenerative Medicine of the Japan Agency for Medical Research and Development (AMED, 19bm0404058h0001), and the Grant-in-Aid for Scientific Research (S) (17K11480) from the Japan Society for the Promotion of Science (JSPS). The corneal research programme at Cardiff University is supported by Fight-for-Sight, the BBSRC and MRC. Y.K. R.H. S.S. and K.N. designed the research. Y.K. and R.H. designed and analyzed the data. Y.K. performed the experiments and acquired the data. Y.K. R.H. and A.J.Q. interpreted the data and wrote the manuscript. R.H. A.J.Q. and K.N. obtained financial support. Funding Information: The authors wish to thank Y. Ishikawa of Osaka University for providing excellent technical support and scientific discussions. This work was supported in part by the Project for the Realization of Regenerative Medicine of the Japan Agency for Medical Research and Development (AMED, 19bm0404058h0001), and the Grant-in-Aid for Scientific Research (S) (17K11480) from the Japan Society for the Promotion of Science (JSPS). The corneal research programme at Cardiff University is supported by Fight-for-Sight, the BBSRC and MRC. Publisher Copyright: {\textcopyright} 2020 The Authors",
year = "2020",
month = jul,
doi = "10.1016/j.scr.2020.101868",
language = "English",
volume = "46",
journal = "Stem Cell Research",
issn = "1873-5061",
publisher = "Elsevier",
}