Modeling preeclampsia using human induced pluripotent stem cells

Abstract Preeclampsia (PE) is a pregnancy-specific hypertensive disorder, affecting up to 10% of pregnancies worldwide. The primary etiology is considered to be abnormal development and function of placental cells called trophoblasts. We previously developed a two-step protocol for differentiation o...

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Autores principales:	Mariko Horii, Robert Morey, Tony Bui, Ojeni Touma, Katharine K. Nelson, Hee-Young Cho, Hannah Rishik, Louise C. Laurent, Mana M. Parast
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/5b11f81d8b0144a4b6f42f04eac8354b
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spelling	oai:doaj.org-article:5b11f81d8b0144a4b6f42f04eac8354b2021-12-02T13:17:56ZModeling preeclampsia using human induced pluripotent stem cells10.1038/s41598-021-85230-52045-2322https://doaj.org/article/5b11f81d8b0144a4b6f42f04eac8354b2021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-85230-5https://doaj.org/toc/2045-2322Abstract Preeclampsia (PE) is a pregnancy-specific hypertensive disorder, affecting up to 10% of pregnancies worldwide. The primary etiology is considered to be abnormal development and function of placental cells called trophoblasts. We previously developed a two-step protocol for differentiation of human pluripotent stem cells, first into cytotrophoblast (CTB) progenitor-like cells, and then into both syncytiotrophoblast (STB)- and extravillous trophoblast (EVT)-like cells, and showed that it can model both normal and abnormal trophoblast differentiation. We have now applied this protocol to induced pluripotent stem cells (iPSC) derived from placentas of pregnancies with or without PE. While there were no differences in CTB induction or EVT formation, PE-iPSC-derived trophoblast showed a defect in syncytialization, as well as a blunted response to hypoxia. RNAseq analysis showed defects in STB formation and response to hypoxia; however, DNA methylation changes were minimal, corresponding only to changes in response to hypoxia. Overall, PE-iPSC recapitulated multiple defects associated with placental dysfunction, including a lack of response to decreased oxygen tension. This emphasizes the importance of the maternal microenvironment in normal placentation, and highlights potential pathways that can be targeted for diagnosis or therapy, while absence of marked DNA methylation changes suggests that other regulatory mechanisms mediate these alterations.Mariko HoriiRobert MoreyTony BuiOjeni ToumaKatharine K. NelsonHee-Young ChoHannah RishikLouise C. LaurentMana M. ParastNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-16 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Mariko Horii Robert Morey Tony Bui Ojeni Touma Katharine K. Nelson Hee-Young Cho Hannah Rishik Louise C. Laurent Mana M. Parast Modeling preeclampsia using human induced pluripotent stem cells
description	Abstract Preeclampsia (PE) is a pregnancy-specific hypertensive disorder, affecting up to 10% of pregnancies worldwide. The primary etiology is considered to be abnormal development and function of placental cells called trophoblasts. We previously developed a two-step protocol for differentiation of human pluripotent stem cells, first into cytotrophoblast (CTB) progenitor-like cells, and then into both syncytiotrophoblast (STB)- and extravillous trophoblast (EVT)-like cells, and showed that it can model both normal and abnormal trophoblast differentiation. We have now applied this protocol to induced pluripotent stem cells (iPSC) derived from placentas of pregnancies with or without PE. While there were no differences in CTB induction or EVT formation, PE-iPSC-derived trophoblast showed a defect in syncytialization, as well as a blunted response to hypoxia. RNAseq analysis showed defects in STB formation and response to hypoxia; however, DNA methylation changes were minimal, corresponding only to changes in response to hypoxia. Overall, PE-iPSC recapitulated multiple defects associated with placental dysfunction, including a lack of response to decreased oxygen tension. This emphasizes the importance of the maternal microenvironment in normal placentation, and highlights potential pathways that can be targeted for diagnosis or therapy, while absence of marked DNA methylation changes suggests that other regulatory mechanisms mediate these alterations.
format	article
author	Mariko Horii Robert Morey Tony Bui Ojeni Touma Katharine K. Nelson Hee-Young Cho Hannah Rishik Louise C. Laurent Mana M. Parast
author_facet	Mariko Horii Robert Morey Tony Bui Ojeni Touma Katharine K. Nelson Hee-Young Cho Hannah Rishik Louise C. Laurent Mana M. Parast
author_sort	Mariko Horii
title	Modeling preeclampsia using human induced pluripotent stem cells
title_short	Modeling preeclampsia using human induced pluripotent stem cells
title_full	Modeling preeclampsia using human induced pluripotent stem cells
title_fullStr	Modeling preeclampsia using human induced pluripotent stem cells
title_full_unstemmed	Modeling preeclampsia using human induced pluripotent stem cells
title_sort	modeling preeclampsia using human induced pluripotent stem cells
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/5b11f81d8b0144a4b6f42f04eac8354b
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Modeling preeclampsia using human induced pluripotent stem cells

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