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Characterization of Endoplasmic Reticulum (ER) in Human Pluripotent Stem Cells Revealed Increased Susceptibility to Cell Death upon ER Stress
Human pluripotent stem cells (hPSCs), such as embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), have a well-orchestrated program for differentiation and self-renewal. However, the structural features of unique proteostatic-maintaining mechanisms in hPSCs and their features, dis...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7291192/ https://www.ncbi.nlm.nih.gov/pubmed/32357563 http://dx.doi.org/10.3390/cells9051078 |
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author | Ha, Tae Won Jeong, Ji Hun Shin, HyeonSeok Kim, Hyun Kyu Im, Jeong Suk Song, Byung Hoo Hanna, Jacob Oh, Jae Sang Woo, Dong-Hun Han, Jaeseok Lee, Man Ryul |
author_facet | Ha, Tae Won Jeong, Ji Hun Shin, HyeonSeok Kim, Hyun Kyu Im, Jeong Suk Song, Byung Hoo Hanna, Jacob Oh, Jae Sang Woo, Dong-Hun Han, Jaeseok Lee, Man Ryul |
author_sort | Ha, Tae Won |
collection | PubMed |
description | Human pluripotent stem cells (hPSCs), such as embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), have a well-orchestrated program for differentiation and self-renewal. However, the structural features of unique proteostatic-maintaining mechanisms in hPSCs and their features, distinct from those of differentiated cells, in response to cellular stress remain unclear. We evaluated and compared the morphological features and stress response of hPSCs and fibroblasts. Compared to fibroblasts, electron microscopy showed simpler/fewer structures with fewer networks in the endoplasmic reticulum (ER) of hPSCs, as well as lower expression of ER-related genes according to meta-analysis. As hPSCs contain low levels of binding immunoglobulin protein (BiP), an ER chaperone, thapsigargin treatment sharply increased the gene expression of the unfolded protein response. Thus, hPSCs with decreased chaperone function reacted sensitively to ER stress and entered apoptosis faster than fibroblasts. Such ER stress-induced apoptotic processes were abolished by tauroursodeoxycholic acid, an ER-stress reliever. Hence, our results revealed that as PSCs have an underdeveloped structure and express fewer BiP chaperone proteins than somatic cells, they are more susceptible to ER stress-induced apoptosis in response to stress. |
format | Online Article Text |
id | pubmed-7291192 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-72911922020-06-17 Characterization of Endoplasmic Reticulum (ER) in Human Pluripotent Stem Cells Revealed Increased Susceptibility to Cell Death upon ER Stress Ha, Tae Won Jeong, Ji Hun Shin, HyeonSeok Kim, Hyun Kyu Im, Jeong Suk Song, Byung Hoo Hanna, Jacob Oh, Jae Sang Woo, Dong-Hun Han, Jaeseok Lee, Man Ryul Cells Article Human pluripotent stem cells (hPSCs), such as embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), have a well-orchestrated program for differentiation and self-renewal. However, the structural features of unique proteostatic-maintaining mechanisms in hPSCs and their features, distinct from those of differentiated cells, in response to cellular stress remain unclear. We evaluated and compared the morphological features and stress response of hPSCs and fibroblasts. Compared to fibroblasts, electron microscopy showed simpler/fewer structures with fewer networks in the endoplasmic reticulum (ER) of hPSCs, as well as lower expression of ER-related genes according to meta-analysis. As hPSCs contain low levels of binding immunoglobulin protein (BiP), an ER chaperone, thapsigargin treatment sharply increased the gene expression of the unfolded protein response. Thus, hPSCs with decreased chaperone function reacted sensitively to ER stress and entered apoptosis faster than fibroblasts. Such ER stress-induced apoptotic processes were abolished by tauroursodeoxycholic acid, an ER-stress reliever. Hence, our results revealed that as PSCs have an underdeveloped structure and express fewer BiP chaperone proteins than somatic cells, they are more susceptible to ER stress-induced apoptosis in response to stress. MDPI 2020-04-26 /pmc/articles/PMC7291192/ /pubmed/32357563 http://dx.doi.org/10.3390/cells9051078 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Ha, Tae Won Jeong, Ji Hun Shin, HyeonSeok Kim, Hyun Kyu Im, Jeong Suk Song, Byung Hoo Hanna, Jacob Oh, Jae Sang Woo, Dong-Hun Han, Jaeseok Lee, Man Ryul Characterization of Endoplasmic Reticulum (ER) in Human Pluripotent Stem Cells Revealed Increased Susceptibility to Cell Death upon ER Stress |
title | Characterization of Endoplasmic Reticulum (ER) in Human Pluripotent Stem Cells Revealed Increased Susceptibility to Cell Death upon ER Stress |
title_full | Characterization of Endoplasmic Reticulum (ER) in Human Pluripotent Stem Cells Revealed Increased Susceptibility to Cell Death upon ER Stress |
title_fullStr | Characterization of Endoplasmic Reticulum (ER) in Human Pluripotent Stem Cells Revealed Increased Susceptibility to Cell Death upon ER Stress |
title_full_unstemmed | Characterization of Endoplasmic Reticulum (ER) in Human Pluripotent Stem Cells Revealed Increased Susceptibility to Cell Death upon ER Stress |
title_short | Characterization of Endoplasmic Reticulum (ER) in Human Pluripotent Stem Cells Revealed Increased Susceptibility to Cell Death upon ER Stress |
title_sort | characterization of endoplasmic reticulum (er) in human pluripotent stem cells revealed increased susceptibility to cell death upon er stress |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7291192/ https://www.ncbi.nlm.nih.gov/pubmed/32357563 http://dx.doi.org/10.3390/cells9051078 |
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