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Whole transcriptome profiling of placental pathobiology in SARS-CoV-2 pregnancies identifies a preeclampsia-like gene signature

Nataly Stylianou, Ismail Sebina, Nicholas Matigian, James Monkman, Hadeel Doehler, Joan Röhl, Mark Allenby, Andy Nam, Liuliu Pan, View ORCID ProfileAnja Rockstroh, Habib Sadeghirad, Kimberly Chung, Thais Sobanski, Ken O’Byrne, Patricia Zadorosnei Rebutini, Cleber Machado-Souza, Emanuele Therezinha Schueda Stonoga, Majid E Warkiani, Carlos Salomon, View ORCID ProfileKirsty Short, Lana McClements, Lucia de Noronha, Ruby Huang, Gabrielle T. Belz, Fernando Souza-Fonseca-Guimaraes, View ORCID ProfileVicki Clifton, View ORCID ProfileArutha Kulasinghe
doi: https://doi.org/10.1101/2023.01.20.524893
Nataly Stylianou
1Centre for Genomics and Personalised Health, School of Biomedical Sciences, Queensland University of Technology, Brisbane, QLD 4102, Australia
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Ismail Sebina
2QIMR Berghofer Medical Research Institute, Herston, Queensland 4006, Australia
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Nicholas Matigian
3QCIF Bioinformatics, St Lucia, QLD 4102, Australia
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James Monkman
4Frazer Institute, Faculty of Medicine, The University of Queensland, Brisbane, QLD 4102, Australia
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Hadeel Doehler
1Centre for Genomics and Personalised Health, School of Biomedical Sciences, Queensland University of Technology, Brisbane, QLD 4102, Australia
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Joan Röhl
5Faculty of Health Sciences and Medicine, Bond University, Queensland, Australia
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Mark Allenby
6BioMimetic Systems Engineering Lab, School of Chemical Engineering, University of Queensland (UQ), St Lucia, QLD, Australia
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Andy Nam
7Nanostring Technologies, Inc, Seattle, WA, USA
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Liuliu Pan
7Nanostring Technologies, Inc, Seattle, WA, USA
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Anja Rockstroh
1Centre for Genomics and Personalised Health, School of Biomedical Sciences, Queensland University of Technology, Brisbane, QLD 4102, Australia
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  • ORCID record for Anja Rockstroh
Habib Sadeghirad
4Frazer Institute, Faculty of Medicine, The University of Queensland, Brisbane, QLD 4102, Australia
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Kimberly Chung
4Frazer Institute, Faculty of Medicine, The University of Queensland, Brisbane, QLD 4102, Australia
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Thais Sobanski
1Centre for Genomics and Personalised Health, School of Biomedical Sciences, Queensland University of Technology, Brisbane, QLD 4102, Australia
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Ken O’Byrne
1Centre for Genomics and Personalised Health, School of Biomedical Sciences, Queensland University of Technology, Brisbane, QLD 4102, Australia
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Patricia Zadorosnei Rebutini
8Postgraduate Program of Health Sciences, School of Medicine, Pontifícia Universidade Católica do Paraná -PUCPR, Curitiba, Brazil
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Cleber Machado-Souza
9Postgraduate Program in Biotechnology Applied in Health of Children and Adolescent, Instituto de Pesquisa Pelé Pequeno Príncipe, Faculdades Pequeno Príncipe, Curitiba, Brazil
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Emanuele Therezinha Schueda Stonoga
10Department of Medical Pathology, Clinical Hospital, Universidade Federal do Paraná -UFPR, Curitiba, Brazil
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Majid E Warkiani
11School of Life Sciences & Institute for Biomedical Materials and Devices, Faculty of Science, University of Technology Sydney, NSW, Australia
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Carlos Salomon
12Exosome Biology Laboratory, Centre for Clinical Diagnostics, University of Queensland Centre for Clinical Research, Royal Brisbane and Women’s Hospital, Faculty of Medicine, The University of Queensland, Brisbane, Australia
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Kirsty Short
13School of Chemistry and Molecular Biosciences, Faculty of Science, The University of Queensland, St Lucia QLD 4067, Australia
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Lana McClements
11School of Life Sciences & Institute for Biomedical Materials and Devices, Faculty of Science, University of Technology Sydney, NSW, Australia
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Lucia de Noronha
8Postgraduate Program of Health Sciences, School of Medicine, Pontifícia Universidade Católica do Paraná -PUCPR, Curitiba, Brazil
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Ruby Huang
14School of Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
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Gabrielle T. Belz
4Frazer Institute, Faculty of Medicine, The University of Queensland, Brisbane, QLD 4102, Australia
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Fernando Souza-Fonseca-Guimaraes
4Frazer Institute, Faculty of Medicine, The University of Queensland, Brisbane, QLD 4102, Australia
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Vicki Clifton
15Mater Medical Research Institute – University of Queensland, Brisbane, Australia
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Arutha Kulasinghe
4Frazer Institute, Faculty of Medicine, The University of Queensland, Brisbane, QLD 4102, Australia
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  • For correspondence: Arutha.kulasinghe@uq.edu.au
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Abstract

In recent years, pregnant people infected with the SARS-CoV-2 virus have shown a higher incidence of “preeclampsia-like syndrome”. Preeclampsia is a systematic syndrome that affects 5-8 % of pregnant people worldwide and is the leading cause of maternal mortality and morbidity. It is unclear what causes preeclampsia, and is characterised by placental dysfunction, leading to poor placental perfusion, maternal hypertension, proteinuria, thrombocytopenia, or neurological disturbances.

In this study, we used whole-transcriptome, digital spatial profiling of placental tissues to analyse the expression of genes at the cellular level between placentae from pregnant participants who contracted SARS-CoV-2 in the third trimester of their pregnancy and those prior to the start of the pandemic. Our focused analysis of the trophoblast and villous core stromal cell populations revealed tissue-specific pathways enriched in the SARS-CoV-2 placentae that align with a pre-eclampsia signature. Most notably, we found enrichment of pathways involved in vascular tension, blood pressure, inflammation, and oxidative stress.

This study illustrates how spatially resolved transcriptomic analysis of placental tissue can aid in understanding the underlying pathogenic mechanisms of SARS-CoV-2 in pregnancy that are thought to induce “preeclampsia-like syndrome”. Moreover, our study highlights the benefits of using digital spatial profiling to map the crosstalk between trophoblast and villous core stromal cells linked to pathways involved in “preeclampsia-like syndrome” presenting in pregnant people with SARS-CoV-2.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-ND 4.0 International license.
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Posted January 21, 2023.
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Whole transcriptome profiling of placental pathobiology in SARS-CoV-2 pregnancies identifies a preeclampsia-like gene signature
Nataly Stylianou, Ismail Sebina, Nicholas Matigian, James Monkman, Hadeel Doehler, Joan Röhl, Mark Allenby, Andy Nam, Liuliu Pan, Anja Rockstroh, Habib Sadeghirad, Kimberly Chung, Thais Sobanski, Ken O’Byrne, Patricia Zadorosnei Rebutini, Cleber Machado-Souza, Emanuele Therezinha Schueda Stonoga, Majid E Warkiani, Carlos Salomon, Kirsty Short, Lana McClements, Lucia de Noronha, Ruby Huang, Gabrielle T. Belz, Fernando Souza-Fonseca-Guimaraes, Vicki Clifton, Arutha Kulasinghe
bioRxiv 2023.01.20.524893; doi: https://doi.org/10.1101/2023.01.20.524893
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Whole transcriptome profiling of placental pathobiology in SARS-CoV-2 pregnancies identifies a preeclampsia-like gene signature
Nataly Stylianou, Ismail Sebina, Nicholas Matigian, James Monkman, Hadeel Doehler, Joan Röhl, Mark Allenby, Andy Nam, Liuliu Pan, Anja Rockstroh, Habib Sadeghirad, Kimberly Chung, Thais Sobanski, Ken O’Byrne, Patricia Zadorosnei Rebutini, Cleber Machado-Souza, Emanuele Therezinha Schueda Stonoga, Majid E Warkiani, Carlos Salomon, Kirsty Short, Lana McClements, Lucia de Noronha, Ruby Huang, Gabrielle T. Belz, Fernando Souza-Fonseca-Guimaraes, Vicki Clifton, Arutha Kulasinghe
bioRxiv 2023.01.20.524893; doi: https://doi.org/10.1101/2023.01.20.524893

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