Whole transcriptome profiling of placental pathobiology in SARS-CoV-2 pregnancies identifies placental dysfunction signatures.

Stylianou, N; Sebina, I; Matigian, N; Monkman, J; Doehler, H; Röhl, J; Allenby, M; Nam, A; Pan, L; Rockstroh, A; Sadeghirad, H; Chung, K; Sobanski, T; O'Byrne, K; Almeida, ACSF; Rebutini, PZ; Machado-Souza, C; Stonoga, ETS; Warkiani, ME; Salomon, C; Short, K; McClements, L; de Noronha, L; Huang, R; Belz, GT; Souza-Fonseca-Guimaraes, F; Clifton, V; Kulasinghe, A

Whole transcriptome profiling of placental pathobiology in SARS-CoV-2 pregnancies identifies placental dysfunction signatures.

Stylianou, N Sebina, I Matigian, N Monkman, J Doehler, H Röhl, J Allenby, M Nam, A Pan, L Rockstroh, A Sadeghirad, H Chung, K Sobanski, T O'Byrne, K Almeida, ACSF Rebutini, PZ Machado-Souza, C Stonoga, ETS Warkiani, ME Salomon, C Short, K McClements, L

de Noronha, L Huang, R Belz, GT Souza-Fonseca-Guimaraes, F Clifton, V Kulasinghe, A

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Publisher:: Wiley
Publication Type:: Journal Article
Citation:: Clin Transl Immunology, 2024, 13, (2), pp. e1488
Issue Date:: 2024

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Field	Value	Language
dc.contributor.author	Stylianou, N
dc.contributor.author	Sebina, I
dc.contributor.author	Matigian, N
dc.contributor.author	Monkman, J
dc.contributor.author	Doehler, H
dc.contributor.author	Röhl, J
dc.contributor.author	Allenby, M
dc.contributor.author	Nam, A
dc.contributor.author	Pan, L
dc.contributor.author	Rockstroh, A
dc.contributor.author	Sadeghirad, H
dc.contributor.author	Chung, K
dc.contributor.author	Sobanski, T
dc.contributor.author	O'Byrne, K
dc.contributor.author	Almeida, ACSF
dc.contributor.author	Rebutini, PZ
dc.contributor.author	Machado-Souza, C
dc.contributor.author	Stonoga, ETS
dc.contributor.author	Warkiani, ME
dc.contributor.author	Salomon, C
dc.contributor.author	Short, K
dc.contributor.author	McClements, L https://orcid.org/0000-0002-4911-1014
dc.contributor.author	de Noronha, L
dc.contributor.author	Huang, R
dc.contributor.author	Belz, GT
dc.contributor.author	Souza-Fonseca-Guimaraes, F
dc.contributor.author	Clifton, V
dc.contributor.author	Kulasinghe, A
dc.date.accessioned	2024-02-12T05:52:40Z
dc.date.available	2024-01-18
dc.date.available	2024-02-12T05:52:40Z
dc.date.issued	2024
dc.identifier.citation	Clin Transl Immunology, 2024, 13, (2), pp. e1488
dc.identifier.issn	2050-0068
dc.identifier.issn	2050-0068
dc.identifier.uri	http://hdl.handle.net/10453/175580
dc.description.abstract	OBJECTIVES: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) virus infection in pregnancy is associated with higher incidence of placental dysfunction, referred to by a few studies as a 'preeclampsia-like syndrome'. However, the mechanisms underpinning SARS-CoV-2-induced placental malfunction are still unclear. Here, we investigated whether the transcriptional architecture of the placenta is altered in response to SARS-CoV-2 infection. METHODS: We utilised whole-transcriptome, digital spatial profiling, to examine gene expression patterns in placental tissues from participants who contracted SARS-CoV-2 in the third trimester of their pregnancy (n = 7) and those collected prior to the start of the coronavirus disease 2019 (COVID-19) pandemic (n = 9). RESULTS: Through comprehensive spatial transcriptomic analyses of the trophoblast and villous core stromal cell subpopulations in the placenta, we identified SARS-CoV-2 to promote signatures associated with hypoxia and placental dysfunction. Notably, genes associated with vasodilation (NOS3), oxidative stress (GDF15, CRH) and preeclampsia (FLT1, EGFR, KISS1, PAPPA2) were enriched with SARS-CoV-2. Pathways related to increased nutrient uptake, vascular tension, hypertension and inflammation were also enriched in SARS-CoV-2 samples compared to uninfected controls. CONCLUSIONS: Our findings demonstrate the utility of spatially resolved transcriptomic analysis in defining the underlying pathogenic mechanisms of SARS-CoV-2 in pregnancy, particularly its role in placental dysfunction. Furthermore, this study highlights the significance of digital spatial profiling in mapping the intricate crosstalk between trophoblasts and villous core stromal cells, thus shedding light on pathways associated with placental dysfunction in pregnancies with SARS-CoV-2 infection.
dc.format	Electronic-eCollection
dc.language	eng
dc.publisher	Wiley
dc.relation.ispartof	Clin Transl Immunology
dc.relation.isbasedon	10.1002/cti2.1488
dc.rights	info:eu-repo/semantics/openAccess
dc.subject	1107 Immunology, 1115 Pharmacology and Pharmaceutical Sciences
dc.subject.classification	3204 Immunology
dc.title	Whole transcriptome profiling of placental pathobiology in SARS-CoV-2 pregnancies identifies placental dysfunction signatures.
dc.type	Journal Article
utslib.citation.volume	13
utslib.location.activity	Australia
utslib.for	1107 Immunology
utslib.for	1115 Pharmacology and Pharmaceutical Sciences
pubs.organisational-group	University of Technology Sydney
pubs.organisational-group	University of Technology Sydney/Faculty of Engineering and Information Technology
pubs.organisational-group	University of Technology Sydney/Faculty of Science
pubs.organisational-group	University of Technology Sydney/Strength - CHT - Health Technologies
pubs.organisational-group	University of Technology Sydney/Faculty of Science/School of Life Sciences
pubs.organisational-group	University of Technology Sydney/Faculty of Engineering and Information Technology/School of Biomedical Engineering
pubs.organisational-group	University of Technology Sydney/Centre for Health Technologies (CHT)
utslib.copyright.status	open_access	*
dc.date.updated	2024-02-12T05:52:30Z
pubs.issue	2
pubs.publication-status	Published online
pubs.volume	13
utslib.citation.issue	2

Abstract:

OBJECTIVES: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) virus infection in pregnancy is associated with higher incidence of placental dysfunction, referred to by a few studies as a 'preeclampsia-like syndrome'. However, the mechanisms underpinning SARS-CoV-2-induced placental malfunction are still unclear. Here, we investigated whether the transcriptional architecture of the placenta is altered in response to SARS-CoV-2 infection. METHODS: We utilised whole-transcriptome, digital spatial profiling, to examine gene expression patterns in placental tissues from participants who contracted SARS-CoV-2 in the third trimester of their pregnancy (n = 7) and those collected prior to the start of the coronavirus disease 2019 (COVID-19) pandemic (n = 9). RESULTS: Through comprehensive spatial transcriptomic analyses of the trophoblast and villous core stromal cell subpopulations in the placenta, we identified SARS-CoV-2 to promote signatures associated with hypoxia and placental dysfunction. Notably, genes associated with vasodilation (NOS3), oxidative stress (GDF15, CRH) and preeclampsia (FLT1, EGFR, KISS1, PAPPA2) were enriched with SARS-CoV-2. Pathways related to increased nutrient uptake, vascular tension, hypertension and inflammation were also enriched in SARS-CoV-2 samples compared to uninfected controls. CONCLUSIONS: Our findings demonstrate the utility of spatially resolved transcriptomic analysis in defining the underlying pathogenic mechanisms of SARS-CoV-2 in pregnancy, particularly its role in placental dysfunction. Furthermore, this study highlights the significance of digital spatial profiling in mapping the intricate crosstalk between trophoblasts and villous core stromal cells, thus shedding light on pathways associated with placental dysfunction in pregnancies with SARS-CoV-2 infection.

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http://hdl.handle.net/10453/175580