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Gene expression profiling of pregnant and virgin mouse lung and liver

ABSTRACT: Metastasis depends on the ability of tumor cells to establish a relationship with the newly seeded host tissue that is conducive to their survival and proliferation. Recent evidence suggests that tumor cells regulate their own dissemination by preparing permissive “metastatic niches” within host tissues. However, the factors that are implicated in rendering tissues permissive for metastatic tumor growth have yet to be fully elucidated. Breast tumors arising during pregnancy display highly aggressive behaviour and early metastatic proclivity, raising the possibility that pregnancy may constitute a physiological condition of permissiveness for tumor dissemination. We show that during murine gestation, both the rate and degree of metastatic tumor growth are enhanced irrespective of tumor type and that decreased natural killer (NK) cell activity is responsible for the observed increase in experimental metastasis. We identify gene expression changes in pregnant mouse lung and liver that bear striking similarity with reported pre-metastatic niche signatures and several of the up-regulated genes are indicative of myeloid-cell infiltration. We provide evidence, that CD11b+ Gr-1+ myeloid-derived suppressor cells accumulate in pregnant mice and exert an inhibitory effect on NK cell activity, thereby enhancing metastatic tumor growth. MDSC have never been evoked in the context of pregnancy and our observations suggest that they may represent a further shared mechanism of immune suppression occurring during gestation and tumor growth.

ORGANISM(S): Mus musculus

PROVIDER: GSE18907 | GEO | 2011/03/19

SECONDARY ACCESSION(S): PRJNA121319

REPOSITORIES: GEO

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Gene expression profiling of pregnant and virgin mouse lung and liver

Project description:Metastasis depends on the ability of tumor cells to establish a relationship with the newly seeded host tissue that is conducive to their survival and proliferation. Recent evidence suggests that tumor cells regulate their own dissemination by preparing permissive “metastatic niches” within host tissues. However, the factors that are implicated in rendering tissues permissive for metastatic tumor growth have yet to be fully elucidated. Breast tumors arising during pregnancy display highly aggressive behaviour and early metastatic proclivity, raising the possibility that pregnancy may constitute a physiological condition of permissiveness for tumor dissemination. We show that during murine gestation, both the rate and degree of metastatic tumor growth are enhanced irrespective of tumor type and that decreased natural killer (NK) cell activity is responsible for the observed increase in experimental metastasis. We identify gene expression changes in pregnant mouse lung and liver that bear striking similarity with reported pre-metastatic niche signatures and several of the up-regulated genes are indicative of myeloid-cell infiltration. We provide evidence, that CD11b+ Gr-1+ myeloid-derived suppressor cells accumulate in pregnant mice and exert an inhibitory effect on NK cell activity, thereby enhancing metastatic tumor growth. MDSC have never been evoked in the context of pregnancy and our observations suggest that they may represent a further shared mechanism of immune suppression occurring during gestation and tumor growth. Three chips were done per organ (liver/lung) and per condition (virgin/pregnant), with equal amounts of RNA from two mice pooled for one chip.

2011-03-19 | E-GEOD-18907 | biostudies-arrayexpress

Uterine transcriptome in b2m KO mice

Project description:Natural killer (NK) cell function is enhanced by interaction of inhibitory NK receptors with MHC class I molecules. NK cell function is critical during placentation, where these cells mediate adaptations to pregnancy in concert with other cells at the maternal/fetal interface. The aim of this experiment was to determine the downstream consequences on the uterine transcriptome that arise from lack of NK interaction with MHC class I molecules. This was done in mice lacking beta-2-microglobulin, thus not having correctly folded surface MHC class I. Biopsies were obtained from the mesometrial poles of the implantation chamber in gestation day (gd) 10.5 pregnant mice.

2018-11-01 | E-MTAB-4727 | biostudies-arrayexpress

Proteomics of early pregnancy maternal serum from preeclampsia and normal pregnancies

Project description:We performed a LC-FAIMS-MS proteomics of early pregnancy (11–14 weeks of gestation) serum from the pregnant women who developed preeclampsia (n = 11) and those from the noraml pregnant women (n = 12).

2022-12-16 | PXD038873 | iProX

The platelet releasate (PR) in human pregnancy

Project description:Healthy pregnancy is characterized by an increase in platelet activation and a decrease in the number of circulating platelets with gestation. Despite this recognised importance, proteomic studies investigating platelets in healthy pregnancy have not been performed. As platelet cargo can be altered in different conditions, we hypothesised that platelets may store a relevant and bespoke collection of molecules during pregnancy. To examine this, we performed comparative label-free quantitative proteomic profiling of platelet releasates from healthy pregnant and non-pregnant women using a tandem mass spectrometry approach. Of the 723 proteins identified, 69 PR proteins were found to be differentially released from platelets in pregnancy, including proteins only expressed during pregnancy such as pregnancy-specific glycoproteins and human placental lactogen.

2020-06-05 | PXD009361 | Pride

Zika virus impacts extracellular vesicle composition and cellular gene expression in macaque early gestation trophoblasts

Project description:Zika virus (ZIKV) infection at the maternal-placental interface is associated with adverse pregnancy outcomes including fetal demise and pregnancy loss. To determine how infection impacts placental trophoblasts, we utilized rhesus macaque trophoblast stem cells (TSC) that can be differentiated into early gestation syncytiotrophoblasts (ST) and extravillous trophoblasts (EVT). TSCs and STs, but not EVTs, were highly permissive to productive infection with ZIKV strain DAK AR 41524. The impact of ZIKV on the cellular transcriptome showed that infection of TSCs and STs increased expression of immune related genes, including those involved in type I and type III interferon responses. ZIKV exposure altered extracellular vesicle (EV) protein, mRNA, and miRNA cargo, regardless of productive infection. These findings suggest that early gestation macaque TSCs and STs are permissive to ZIKV infection, and that EV analysis may provide a foundation for identifying non-invasive biomarkers of placental infection in a highly translational model.

2022-05-20 | PXD033289 | Pride

Gene expression profiles of p53 depleted human mammary epithelial cells with their Ras-infected epithelial and mesenchymal derivatives

Project description:The epithelial-mesenchymal transition (EMT) is an embryonic transdiffrentiation program which consists of the conversion of polarized epithelial cells into a motile mesenchymal phenotype. EMT is aberrantly reactivated during tumor progression, promoting metastatic dissemination. Herein, we demonstrate that EMT permissive conditions also favor tumor initiation by minimizing the number of events required for neoplastic transformation. We further demonstrated that even partial commitment of human mammary epithelial cells into an EMT program is sufficient to confer malignant properties, suggesting that the reactivation of embryonic EMT inducers participate to the primary tumor growth long before the initiation of the invasion-metastasis cascade.

2012-01-31 | GSE26541 | GEO

Genomic profiling of human Tert/shp53/Ras mesenchymal cells isolated from several xenografted tumors and their non-transformant epithelial counterparts

Project description:The epithelial-mesenchymal transition (EMT) is an embryonic transdifferentiation program which consists of the conversion of polarized epithelial cells into a motile mesenchymal phenotype. EMT is aberrantly reactivated during tumor progression, promoting metastatic dissemination. Herein, we demonstrate that EMT-permissive conditions also favor tumor initiation by minimizing the number of events required for neoplastic transformation. We further demonstrated that even the partial commitment of human mammary epithelial cells into an EMT program is sufficient to confer malignant properties, suggesting that the reactivation of embryonic EMT inducers participates to the primary tumor growth long before the initiation of the invasion-metastasis cascade.

2011-01-11 | GSE26534 | GEO

Genomic profiling of human Tert/shp53/Ras mesenchymal cells isolated from several xenografted tumors and their non-transformant epithelial counterparts

2011-01-11 | E-GEOD-26534 | biostudies-arrayexpress

Changes in DNA methylation during pregnancy and after delivery

Project description:Peripheral whole blood DNA methylation profiles of pregnant women with normal pregnancy from the 10th-14th weeks of gestation (average at the 10th week), 24th-28th weeks of gestation (average at the 25th week), 38th-40th weeks of gestation (average at the 38th week) and after delivery status (average at the 10th month after delivery)

2022-01-05 | GSE192918 | GEO

Small RNA sequencing of cow's peripheral plasma exosomes

Project description:OBJECTIVE: To reveal the miRNA expression profile of placental exosomes by high-throughput sequencing and screen key biomarkers in different pregnancy period to provide new research ideas for the establishment and maintenance of pregnancy in cows and other ruminants.It can also provide reference for other pregnancy diseases. METHOD: Exosmal miRNAs were isolated from non-pregnant cows（n=3,Gestation Day(G.D.) 0）,early pregnant cows（n=3,G.D.60）,Middile pregnant cows（n=3,G.D.150）,Late pregnant cows（n=3,G.D.240）, small RNA profiles were generated by deep sequencing, in triplicate, using Illumina Hiseq SE50. RESULTS: During pregnancy, there was a high quantity of placental exosomes in the peripheral blood of cows, which selectively loaded some miRNAs. The abundance and species of miRNAs various from different stages of pregnancy, suggesting that exosomal miRNAs is involved in the regulation mechanism of pregnancy.

2018-06-21 | GSE110324 | GEO

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