High glucose causes developmental abnormalities in neuroepithelial cysts with actin and HK1 distribution changes

It has been reported that the offspring of diabetic pregnant women have an increased risk for neural tube defects. Previous studies in animal models suggested that high glucose induces cell apoptosis and epigenetic changes in the developing neural tube. However, effects on other cellular aspects suc...

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Main Authors: Sisi Peng, Yu Wu, Yufang Zheng
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-01-01
Series:Frontiers in Cell and Developmental Biology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fcell.2022.1021284/full
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author Sisi Peng
Sisi Peng
Sisi Peng
Yu Wu
Yu Wu
Yu Wu
Yufang Zheng
Yufang Zheng
Yufang Zheng
author_facet Sisi Peng
Sisi Peng
Sisi Peng
Yu Wu
Yu Wu
Yu Wu
Yufang Zheng
Yufang Zheng
Yufang Zheng
author_sort Sisi Peng
collection DOAJ
description It has been reported that the offspring of diabetic pregnant women have an increased risk for neural tube defects. Previous studies in animal models suggested that high glucose induces cell apoptosis and epigenetic changes in the developing neural tube. However, effects on other cellular aspects such as the cell shape changes were not fully investigated. Actin dynamics plays essential roles in cell shape change. Disruption on actin dynamics is known to cause neural tube defects. In the present study, we used a 3D neuroepithelial cyst model and a rosette model, both cultured from human embryonic stem cells, to study the cellular effects caused by high glucose. By using these models, we observed couple of new changes besides increased apoptosis. First, we observed that high glucose disturbed the distribution of pH3 positive cells in the neuroepithelial cysts. Secondly, we found that high glucose exposure caused a relatively smaller actin inner boundary enclosed area, which was unlikely due to osmolarity changes. We further investigated key glucose metabolic enzymes in our models and the results showed that the distribution of hexokinase1 (HK1) was affected by high glucose. We observed that hexokinase1 has an apical-basal polarized distribution and is highest next to actin at the boundaries. hexokinase1 was more diffused and distributed less polarized under high glucose condition. Together, our observations broadened the cellular effects that may be caused by high glucose in the developing neural tube, especially in the secondary neurulation process.
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spelling doaj.art-d16f754037944617bbbbb6f143eaa09a2023-01-06T14:28:29ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2023-01-011010.3389/fcell.2022.10212841021284High glucose causes developmental abnormalities in neuroepithelial cysts with actin and HK1 distribution changesSisi Peng0Sisi Peng1Sisi Peng2Yu Wu3Yu Wu4Yu Wu5Yufang Zheng6Yufang Zheng7Yufang Zheng8Department of Cellular and Developmental Biology, School of Life Sciences, Fudan University, Shanghai, ChinaObstetrics and Gynecology Hospital, The Institute of Obstetrics and Gynecology, Fudan University, Shanghai, ChinaState Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, ChinaDepartment of Cellular and Developmental Biology, School of Life Sciences, Fudan University, Shanghai, ChinaObstetrics and Gynecology Hospital, The Institute of Obstetrics and Gynecology, Fudan University, Shanghai, ChinaState Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, ChinaDepartment of Cellular and Developmental Biology, School of Life Sciences, Fudan University, Shanghai, ChinaObstetrics and Gynecology Hospital, The Institute of Obstetrics and Gynecology, Fudan University, Shanghai, ChinaState Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, ChinaIt has been reported that the offspring of diabetic pregnant women have an increased risk for neural tube defects. Previous studies in animal models suggested that high glucose induces cell apoptosis and epigenetic changes in the developing neural tube. However, effects on other cellular aspects such as the cell shape changes were not fully investigated. Actin dynamics plays essential roles in cell shape change. Disruption on actin dynamics is known to cause neural tube defects. In the present study, we used a 3D neuroepithelial cyst model and a rosette model, both cultured from human embryonic stem cells, to study the cellular effects caused by high glucose. By using these models, we observed couple of new changes besides increased apoptosis. First, we observed that high glucose disturbed the distribution of pH3 positive cells in the neuroepithelial cysts. Secondly, we found that high glucose exposure caused a relatively smaller actin inner boundary enclosed area, which was unlikely due to osmolarity changes. We further investigated key glucose metabolic enzymes in our models and the results showed that the distribution of hexokinase1 (HK1) was affected by high glucose. We observed that hexokinase1 has an apical-basal polarized distribution and is highest next to actin at the boundaries. hexokinase1 was more diffused and distributed less polarized under high glucose condition. Together, our observations broadened the cellular effects that may be caused by high glucose in the developing neural tube, especially in the secondary neurulation process.https://www.frontiersin.org/articles/10.3389/fcell.2022.1021284/fullhigh glucoseactinHK1neuroepithelial cystsneural rosettes
spellingShingle Sisi Peng
Sisi Peng
Sisi Peng
Yu Wu
Yu Wu
Yu Wu
Yufang Zheng
Yufang Zheng
Yufang Zheng
High glucose causes developmental abnormalities in neuroepithelial cysts with actin and HK1 distribution changes
Frontiers in Cell and Developmental Biology
high glucose
actin
HK1
neuroepithelial cysts
neural rosettes
title High glucose causes developmental abnormalities in neuroepithelial cysts with actin and HK1 distribution changes
title_full High glucose causes developmental abnormalities in neuroepithelial cysts with actin and HK1 distribution changes
title_fullStr High glucose causes developmental abnormalities in neuroepithelial cysts with actin and HK1 distribution changes
title_full_unstemmed High glucose causes developmental abnormalities in neuroepithelial cysts with actin and HK1 distribution changes
title_short High glucose causes developmental abnormalities in neuroepithelial cysts with actin and HK1 distribution changes
title_sort high glucose causes developmental abnormalities in neuroepithelial cysts with actin and hk1 distribution changes
topic high glucose
actin
HK1
neuroepithelial cysts
neural rosettes
url https://www.frontiersin.org/articles/10.3389/fcell.2022.1021284/full
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