Hyperthermia Disturbs and Delays Spontaneous Differentiation of Human Embryoid Bodies

Various types of stress stimuli have been shown to threaten the normal development of embryos during embryogenesis. Prolonged heat exposure is the most common stressor that poses a threat to embryo development. Despite the extensive investigation of heat stress control mechanisms in the cytosol, the...

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Main Authors: Ji Hyun Kwon, Hyun Kyu Kim, Tae Won Ha, Jeong Suk Im, Byung Hoo Song, Ki Sung Hong, Jae Sang Oh, Jaeseok Han, Man Ryul Lee
Format: Article
Language:English
Published: MDPI AG 2020-06-01
Series:Biomedicines
Subjects:
Online Access:https://www.mdpi.com/2227-9059/8/6/176
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author Ji Hyun Kwon
Hyun Kyu Kim
Tae Won Ha
Jeong Suk Im
Byung Hoo Song
Ki Sung Hong
Jae Sang Oh
Jaeseok Han
Man Ryul Lee
author_facet Ji Hyun Kwon
Hyun Kyu Kim
Tae Won Ha
Jeong Suk Im
Byung Hoo Song
Ki Sung Hong
Jae Sang Oh
Jaeseok Han
Man Ryul Lee
author_sort Ji Hyun Kwon
collection DOAJ
description Various types of stress stimuli have been shown to threaten the normal development of embryos during embryogenesis. Prolonged heat exposure is the most common stressor that poses a threat to embryo development. Despite the extensive investigation of heat stress control mechanisms in the cytosol, the endoplasmic reticulum (ER) heat stress response remains unclear. In this study, we used human embryonic stem cells (hESCs) to examine the effect of heat stress on early embryonic development, specifically alterations in the ER stress response. In a hyperthermic (42 °C) culture, ER stress response genes involved in hESC differentiation were induced within 1 h of exposure, which resulted in disturbed and delayed differentiation. In addition, hyperthermia increased the expression levels of activating transcription factor 4 (ATF4) and C/EBP homologous protein (CHOP) genes, which are associated with the protein kinase RNA-like endoplasmic reticulum kinase (PERK) signaling pathway. Furthermore, we demonstrated that tauroursodeoxycholic acid, a chemical chaperone, mitigated the delayed differentiation under hyperthermia. Our study identified novel gene markers in response to hyperthermia-induced ER stress on hESCs, thereby providing further insight into the mechanisms that regulate human embryogenesis.
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spelling doaj.art-2a7e535098e446db8b429078b5364d2e2023-11-20T05:03:49ZengMDPI AGBiomedicines2227-90592020-06-018617610.3390/biomedicines8060176Hyperthermia Disturbs and Delays Spontaneous Differentiation of Human Embryoid BodiesJi Hyun Kwon0Hyun Kyu Kim1Tae Won Ha2Jeong Suk Im3Byung Hoo Song4Ki Sung Hong5Jae Sang Oh6Jaeseok Han7Man Ryul Lee8Soonchunhyang Institute of Medi-bio Science (SIMS), Soon Chun Hyang University, Cheonan 31151, KoreaSoonchunhyang Institute of Medi-bio Science (SIMS), Soon Chun Hyang University, Cheonan 31151, KoreaSoonchunhyang Institute of Medi-bio Science (SIMS), Soon Chun Hyang University, Cheonan 31151, KoreaSoonchunhyang Institute of Medi-bio Science (SIMS), Soon Chun Hyang University, Cheonan 31151, KoreaSoonchunhyang Institute of Medi-bio Science (SIMS), Soon Chun Hyang University, Cheonan 31151, KoreaDepartment of Medicine, Konkuk University School of Medicine and Mirae Cell Bio Co. LTD., Seoul 05029, KoreaDepartment of Neurosurgery, College of Medicine, Soonchunhyang University, Cheonan Hospital, Cheonan 31151, KoreaSoonchunhyang Institute of Medi-bio Science (SIMS), Soon Chun Hyang University, Cheonan 31151, KoreaSoonchunhyang Institute of Medi-bio Science (SIMS), Soon Chun Hyang University, Cheonan 31151, KoreaVarious types of stress stimuli have been shown to threaten the normal development of embryos during embryogenesis. Prolonged heat exposure is the most common stressor that poses a threat to embryo development. Despite the extensive investigation of heat stress control mechanisms in the cytosol, the endoplasmic reticulum (ER) heat stress response remains unclear. In this study, we used human embryonic stem cells (hESCs) to examine the effect of heat stress on early embryonic development, specifically alterations in the ER stress response. In a hyperthermic (42 °C) culture, ER stress response genes involved in hESC differentiation were induced within 1 h of exposure, which resulted in disturbed and delayed differentiation. In addition, hyperthermia increased the expression levels of activating transcription factor 4 (ATF4) and C/EBP homologous protein (CHOP) genes, which are associated with the protein kinase RNA-like endoplasmic reticulum kinase (PERK) signaling pathway. Furthermore, we demonstrated that tauroursodeoxycholic acid, a chemical chaperone, mitigated the delayed differentiation under hyperthermia. Our study identified novel gene markers in response to hyperthermia-induced ER stress on hESCs, thereby providing further insight into the mechanisms that regulate human embryogenesis.https://www.mdpi.com/2227-9059/8/6/176hyperthermiaembryogenesishuman embryonic stem cellsendoplasmic reticulumstress response
spellingShingle Ji Hyun Kwon
Hyun Kyu Kim
Tae Won Ha
Jeong Suk Im
Byung Hoo Song
Ki Sung Hong
Jae Sang Oh
Jaeseok Han
Man Ryul Lee
Hyperthermia Disturbs and Delays Spontaneous Differentiation of Human Embryoid Bodies
Biomedicines
hyperthermia
embryogenesis
human embryonic stem cells
endoplasmic reticulum
stress response
title Hyperthermia Disturbs and Delays Spontaneous Differentiation of Human Embryoid Bodies
title_full Hyperthermia Disturbs and Delays Spontaneous Differentiation of Human Embryoid Bodies
title_fullStr Hyperthermia Disturbs and Delays Spontaneous Differentiation of Human Embryoid Bodies
title_full_unstemmed Hyperthermia Disturbs and Delays Spontaneous Differentiation of Human Embryoid Bodies
title_short Hyperthermia Disturbs and Delays Spontaneous Differentiation of Human Embryoid Bodies
title_sort hyperthermia disturbs and delays spontaneous differentiation of human embryoid bodies
topic hyperthermia
embryogenesis
human embryonic stem cells
endoplasmic reticulum
stress response
url https://www.mdpi.com/2227-9059/8/6/176
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