PAX2 is dispensable for in vitro nephron formation from human induced pluripotent stem cells
Abstract The kidney is formed by reciprocal interactions between the nephron progenitor and the ureteric bud, the former of which gives rise to the epithelia of nephrons consisting of glomeruli and renal tubules. The transcription factor PAX2 is essential for this mesenchymal-to-epithelial transitio...
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Online Access: | https://doi.org/10.1038/s41598-017-04813-3 |
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doaj-5c93a9331aaf4abe88ba9f48b1f8daa12020-12-08T02:23:18ZengNature Publishing GroupScientific Reports2045-23222017-07-017111210.1038/s41598-017-04813-3PAX2 is dispensable for in vitro nephron formation from human induced pluripotent stem cellsYusuke Kaku0Atsuhiro Taguchi1Shunsuke Tanigawa2Fahim Haque3Tetsushi Sakuma4Takashi Yamamoto5Ryuichi Nishinakamura6Department of Kidney Development, Institute of Molecular Embryology and Genetics, Kumamoto UniversityDepartment of Kidney Development, Institute of Molecular Embryology and Genetics, Kumamoto UniversityDepartment of Kidney Development, Institute of Molecular Embryology and Genetics, Kumamoto UniversityDepartment of Kidney Development, Institute of Molecular Embryology and Genetics, Kumamoto UniversityDepartment of Mathematical and Life Sciences, Graduate School of Science, Hiroshima UniversityDepartment of Mathematical and Life Sciences, Graduate School of Science, Hiroshima UniversityDepartment of Kidney Development, Institute of Molecular Embryology and Genetics, Kumamoto UniversityAbstract The kidney is formed by reciprocal interactions between the nephron progenitor and the ureteric bud, the former of which gives rise to the epithelia of nephrons consisting of glomeruli and renal tubules. The transcription factor PAX2 is essential for this mesenchymal-to-epithelial transition of nephron progenitors, as well as ureteric bud lineage development, in mice. PAX2 mutations in humans cause renal coloboma syndrome. We previously reported the induction of nephron progenitors and three-dimensional nephron structures from human induced pluripotent stem (iPS) cells. Here we generate iPS cells lacking PAX2, and address the role of PAX2 in our in vitro induction protocol. While PAX2-null human nephron progenitors were properly formed, they unexpectedly became epithelialised to form glomeruli and renal tubules. However, the mutant glomerular parietal epithelial cells failed to transit to the squamous morphology, retaining the shape and markers of columnar epithelia. Therefore, PAX2 is dispensable for mesenchymal-to-epithelial transition of nephron progenitors, but is required for morphological development of glomerular parietal epithelial cells, during nephron formation from human iPS cells in vitro.https://doi.org/10.1038/s41598-017-04813-3 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Yusuke Kaku Atsuhiro Taguchi Shunsuke Tanigawa Fahim Haque Tetsushi Sakuma Takashi Yamamoto Ryuichi Nishinakamura |
spellingShingle |
Yusuke Kaku Atsuhiro Taguchi Shunsuke Tanigawa Fahim Haque Tetsushi Sakuma Takashi Yamamoto Ryuichi Nishinakamura PAX2 is dispensable for in vitro nephron formation from human induced pluripotent stem cells Scientific Reports |
author_facet |
Yusuke Kaku Atsuhiro Taguchi Shunsuke Tanigawa Fahim Haque Tetsushi Sakuma Takashi Yamamoto Ryuichi Nishinakamura |
author_sort |
Yusuke Kaku |
title |
PAX2 is dispensable for in vitro nephron formation from human induced pluripotent stem cells |
title_short |
PAX2 is dispensable for in vitro nephron formation from human induced pluripotent stem cells |
title_full |
PAX2 is dispensable for in vitro nephron formation from human induced pluripotent stem cells |
title_fullStr |
PAX2 is dispensable for in vitro nephron formation from human induced pluripotent stem cells |
title_full_unstemmed |
PAX2 is dispensable for in vitro nephron formation from human induced pluripotent stem cells |
title_sort |
pax2 is dispensable for in vitro nephron formation from human induced pluripotent stem cells |
publisher |
Nature Publishing Group |
series |
Scientific Reports |
issn |
2045-2322 |
publishDate |
2017-07-01 |
description |
Abstract The kidney is formed by reciprocal interactions between the nephron progenitor and the ureteric bud, the former of which gives rise to the epithelia of nephrons consisting of glomeruli and renal tubules. The transcription factor PAX2 is essential for this mesenchymal-to-epithelial transition of nephron progenitors, as well as ureteric bud lineage development, in mice. PAX2 mutations in humans cause renal coloboma syndrome. We previously reported the induction of nephron progenitors and three-dimensional nephron structures from human induced pluripotent stem (iPS) cells. Here we generate iPS cells lacking PAX2, and address the role of PAX2 in our in vitro induction protocol. While PAX2-null human nephron progenitors were properly formed, they unexpectedly became epithelialised to form glomeruli and renal tubules. However, the mutant glomerular parietal epithelial cells failed to transit to the squamous morphology, retaining the shape and markers of columnar epithelia. Therefore, PAX2 is dispensable for mesenchymal-to-epithelial transition of nephron progenitors, but is required for morphological development of glomerular parietal epithelial cells, during nephron formation from human iPS cells in vitro. |
url |
https://doi.org/10.1038/s41598-017-04813-3 |
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