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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
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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.
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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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