Ocular surface ectoderm instigated by WNT inhibition and BMP4
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...
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doaj-eb70685e8b9644069cc0098897e3c9332020-11-25T03:10:52ZengElsevierStem Cell Research1873-50612020-07-0146101868Ocular surface ectoderm instigated by WNT inhibition and BMP4Yuki Kobayashi0Ryuhei Hayashi1Shun Shibata2Andrew J. Quantock3Kohji Nishida4Department of Ophthalmology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan; Department of Stem Cells and Applied Medicine, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, JapanDepartment of Ophthalmology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan; Department of Stem Cells and Applied Medicine, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan; Corresponding author at: Department of Stem Cells and Applied Medicine, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.Department of Stem Cells and Applied Medicine, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan; Research and Development Division, ROHTO Pharmaceutical Co Ltd, Osaka, Osaka 544-8666, JapanStructural Biophysics Group, School of Optometry and Vision Sciences, College of Biomedical and Life Sciences, Cardiff University, Cardiff, CF24 4HQ Wales, UKDepartment of Ophthalmology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan; Integrated Frontier Research for Medical Science Division, Institute for Open and Transdisciplinary Research Initiatives (OTRI), Osaka University, Suita, Osaka 565-0871, JapanWe 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.http://www.sciencedirect.com/science/article/pii/S1873506120301690Human iPS cellsOcular surface ectodermEpithelial stem cellsCorneal epitheliumWNT signalingBMP4 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Yuki Kobayashi Ryuhei Hayashi Shun Shibata Andrew J. Quantock Kohji Nishida |
spellingShingle |
Yuki Kobayashi Ryuhei Hayashi Shun Shibata Andrew J. Quantock Kohji Nishida Ocular surface ectoderm instigated by WNT inhibition and BMP4 Stem Cell Research Human iPS cells Ocular surface ectoderm Epithelial stem cells Corneal epithelium WNT signaling BMP4 |
author_facet |
Yuki Kobayashi Ryuhei Hayashi Shun Shibata Andrew J. Quantock Kohji Nishida |
author_sort |
Yuki Kobayashi |
title |
Ocular surface ectoderm instigated by WNT inhibition and BMP4 |
title_short |
Ocular surface ectoderm instigated by WNT inhibition and BMP4 |
title_full |
Ocular surface ectoderm instigated by WNT inhibition and BMP4 |
title_fullStr |
Ocular surface ectoderm instigated by WNT inhibition and BMP4 |
title_full_unstemmed |
Ocular surface ectoderm instigated by WNT inhibition and BMP4 |
title_sort |
ocular surface ectoderm instigated by wnt inhibition and bmp4 |
publisher |
Elsevier |
series |
Stem Cell Research |
issn |
1873-5061 |
publishDate |
2020-07-01 |
description |
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. |
topic |
Human iPS cells Ocular surface ectoderm Epithelial stem cells Corneal epithelium WNT signaling BMP4 |
url |
http://www.sciencedirect.com/science/article/pii/S1873506120301690 |
work_keys_str_mv |
AT yukikobayashi ocularsurfaceectoderminstigatedbywntinhibitionandbmp4 AT ryuheihayashi ocularsurfaceectoderminstigatedbywntinhibitionandbmp4 AT shunshibata ocularsurfaceectoderminstigatedbywntinhibitionandbmp4 AT andrewjquantock ocularsurfaceectoderminstigatedbywntinhibitionandbmp4 AT kohjinishida ocularsurfaceectoderminstigatedbywntinhibitionandbmp4 |
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