Human placental gene sets improve analysis of placental pathologies and link trophoblast and cancer invasion genes

Naismith, Kendra; Cox, Brian

doi:10.1016/j.placenta.2021.06.011

Cited by 6 publications

(11 citation statements)

References 38 publications

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“…Interestingly, all four genes have been shown to have roles in cancer cells: Siah2 was shown to promote cell invasiveness in human gastric cancer cells by interacting with ETS2 and TWIST1 [78]; Mtdh regulates proliferation and migration of esophageal squamous cell carcinoma cells [79]; absence of Hnrnpk reduces cell proliferation, migration and invasion ability in human gastric cancer cells [80]; and repression of NCOR2 and ZBTB7A increased cell migration in lung adenocarcinoma cells [81]. This result further supports previous studies that show the comparability between placental cell migration and invasion, and tumor cell migration and invasion [71], [82], although specific genes may have different impacts on migration/invasion capacity such as with the Ncor2 gene. We acknowledge the HTR-8/SVneo cell line bears certain differences to TB cells such as in their miRNA expression profiles [83].…”

Section: Discussionsupporting

confidence: 83%

“…For genes in network e7.5_1_STRING, e9.5_1_STRING, and e9.5_3_GENIE3, we did not observe any enrichment for fetal placental cells, possibly because not all genes in the networks are annotated in the 1 st trimester dataset [70] used when calculating cell enrichments in PlacentaCellEnrich. Therefore, we also used Placenta Ontology [71], which carries out enrichment tests based on different datasets than those used in PlacentaCellEnrich. With e7.5_1_STRING, in agreement with previous analyses on e7.5-specific genes or genes in e7.5_2_GENIE3 network, we observed annotations related to EVT cells being enriched, such as “EVT > side population” (log 2 (fold) = 1.99 and false discovery rate (FDR) = 0.027), and “EVT > CT” (log 2 (fold) = 1.96, FDR = 0.028) (Supplementary Table S9).…”

Section: Resultsmentioning

confidence: 99%

“…The PlacentaCellEnrich webtool [69] and Placenta Ontology [71] were used to infer the relevant cell types using gene lists. For PlacentaCellEnrich, cell-type specific groups were based on the single-cell transcriptome data of human maternal-fetal interface from Vento-Tormo et al [26].…”

Section: Placenta Cell Enrichment and Placenta Ontology Analysismentioning

confidence: 99%

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Identifying novel regulators of placental development using time series transcriptomic data and network analyses

Kaur

Kies

et al. 2022

Preprint

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The placenta serves as a connection between the mother and the fetus during pregnancy, and provides the fetus with oxygen, nutrients, and growth hormones. However, the regulatory mechanisms and dynamic gene interaction networks underlying early placental development are understudied. Here, we generated RNA sequencing (RNA-seq) data from mouse fetal placenta tissues at embryonic day (e) 7.5, e8.5 and e9.5 to identify genes with timepoint-specific expression, then inferred gene interaction networks to analyze highly connected network modules. We determined that timepoint-specific gene network modules associated with distinct developmental processes, and with similar expression profiles to specific human placental cell populations. From each module, we obtained hub genes and their direct neighboring genes, which were predicted to govern placental functions. We confirmed that four novel candidate regulators identified through our analyses regulate cell migration in the HTR-8/SVneo cell line. Upon conclusion of this study, we were able to predict several novel regulators of placental development using network analysis of bulk RNA-seq data. Our findings and analysis approaches will be valuable for future studies investigating the transcriptional landscape of early placental development.

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Section: Discussionsupporting

confidence: 83%

Section: Resultsmentioning

confidence: 99%

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Identifying novel regulators of placental development using time series transcriptomic data and network analyses

Kaur

Kies

et al. 2022

Preprint

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“…For genes in networks e7.5_1_STRING, e9.5_1_STRING, and e9.5_3_GENIE3, we did not observe any enrichment for fetal placental cells, possibly because not all genes in the networks are annotated in the first trimester dataset ( 28 ) used when calculating cell enrichments in PlacentaCellEnrich. Therefore, we also used placenta ontology ( 76 ), which carries out enrichment tests based on different datasets than those used in PlacentaCellEnrich. With e7.5_1_STRING, in agreement with previous analyses on e7.5-specific genes or genes in the e7.5_2_GENIE3 network, we observed annotations related to EVT cells being enriched, such as “EVT > side population” (log 2 [fold] = 1.99 and false discovery rate [FDR] = 0.027) and “EVT > CT” (log 2 [fold] = 1.96 and FDR = 0.028) (Table S8).…”

Section: Resultsmentioning

confidence: 99%

Identifying novel regulators of placental development using time-series transcriptome data

Kaur

Kies

et al. 2022

Life Sci. Alliance

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The placenta serves as a connection between the mother and the fetus during pregnancy, providing the fetus with oxygen, nutrients, and growth hormones. However, the regulatory mechanisms and dynamic gene interaction networks underlying early placental development are understudied. Here, we generated RNA-sequencing data from mouse fetal placenta at embryonic days 7.5, 8.5, and 9.5 to identify genes with timepoint-specific expression, then inferred gene interaction networks to analyze highly connected network modules. We determined that timepoint-specific gene network modules were associated with distinct developmental processes, and with similar expression profiles to specific human placental cell populations. From each module, we identified hub genes and their direct neighboring genes, which were predicted to govern placental functions. We confirmed that four novel candidate regulators identified through our analyses regulate cell migration in the HTR-8/SVneo cell line. Overall, we predicted several novel regulators of placental development expressed in specific placental cell types using network analysis of bulk RNA-sequencing data. Our findings and analysis approaches will be valuable for future studies investigating the transcriptional landscape of early development.

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“…Intrauterine growth restriction (IUGR) in turn, is associated with a heightened risk for adult-onset cardiometabolic diseases, coronary heart disease and stroke, supporting a placental role in long-term health of offspring (Brodszki, Länne, Marsál, & Ley, 2005; Crispi et al, 2010; Cruz-Lemini et al, 2016; Eriksson, Kajantie, Thornburg, & Osmond, 2016; Menendez-Castro, Rascher, & Hartner, 2018; Mierzynski et al, 2016; Morsing, Liuba, Fellman, Maršál, & Brodszki, 2014; Sarvari et al, 2017). Despite the many adverse pregnancy outcomes involving placental defects, the molecular and cellular factors that impact placental development are poorly understood (Naismith & Cox, 2021; Perez-Garcia et al, 2018). Until recently, most studies on the origins of placental pathology have focused on maternal factors.…”

Section: Introductionmentioning

confidence: 99%

Paternal obesity alters the sperm epigenome and is associated with changes in the placental transcriptome and cellular composition

Pépin

Jazwiec

Dumeaux

et al. 2022

Preprint

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Paternal obesity has been implicated in adult-onset metabolic disease in offspring. However, the molecular mechanisms driving these paternal effects and the developmental processes involved remain poorly understood. One underexplored possibility is the role of paternally driven gene expression in placenta function. To address this, we investigated paternal high-fat diet-induced obesity in relation to sperm epigenetic signatures, the placenta transcriptome and cellular composition. C57BL6/J males were fed either a control or high-fat diet for 10 weeks beginning at 6 weeks of age. Males were timed-mated with control-fed C57BL6/J females to generate pregnancies, followed by collection of sperm, and placentas at embryonic day (E)14.5. Chromatin immunoprecipitation targeting histone H3 lysine 4 tri-methylation (H3K4me3) followed by sequencing (ChIP-seq) was performed on sperm to define obesity-associated changes in enrichment. Paternal obesity corresponded with altered sperm H3K4me3 enrichment at imprinted genes, and at promoters of genes involved in metabolism and development. Notably, sperm altered H3K4me3 was localized at placental enhancers and genes implicated in placental development and function. Bulk RNA-sequencing on placentas detected paternal obesity-induced sex-specific changes in gene expression associated with hypoxic processes such as angiogenesis, nutrient transport and imprinted genes. Paternal obesity was also linked to placenta development; specifically, a deconvolution analysis revealed altered trophoblast cell lineage specification. These findings implicate paternal obesity-effects on placenta development and function as one mechanism underlying offspring metabolic disease.

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Human placental gene sets improve analysis of placental pathologies and link trophoblast and cancer invasion genes

Cited by 6 publications

References 38 publications

Identifying novel regulators of placental development using time series transcriptomic data and network analyses

Identifying novel regulators of placental development using time series transcriptomic data and network analyses

Identifying novel regulators of placental development using time-series transcriptome data

Paternal obesity alters the sperm epigenome and is associated with changes in the placental transcriptome and cellular composition

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