Association of dysfunctional synapse defective 1 (SYDE1) with restricted fetal growth – SYDE1 regulates placental cell migration and invasion
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE81468 | GEO | 2016/10/18
SECONDARY ACCESSION(S): PRJNA321728
REPOSITORIES: GEO
Similar Datasets
Project description:Intrauterine growth restriction (IUGR) represents a major obstetric challenge with perinatal complications and a risk factor of developing disease in adult life. Placental insufficiency is one of the common features accompanying IUGR. The aim of this study was to evaluate global placental gene expression profile in IUGR compared to normal pregnancies. Placental samples were collected by eight IUGR pregnancies with placental insufficiency ascertained by Doppler and eight healthy controls. A 30K Human Genome Survey Microarray v.2.0 (Applied Biosystems) was used to evaluate global gene expression profile. Principal component analysis showed good separation in terms of gene expression patterns between the groups. Pathway analysis with Bonferroni correction for multiple testing showed significant (p<0.05) up-regulation of inflammation mediated by chemokine and cytokine signalling pathway in the IUGR placentas. Genes involved in metabolism of glucocorticoids (HSD11B1 and DHRS2) were found differentially expressed. We found no imprinted genes to be differentially expressed and only one gene involved in epigenetic modifications (MBD3) to be down-regulated in the IUGR placentas, indicating that IUGR due to placental insufficiency is not associated to placental imprinting. Subgroup analysis between pure IUGR and IUGR with preeclampsia placentas showed only 27 differentially expressed genes suggesting common pathophysiology. Eight placental samples from normal human placenta compared to eight human placental samples from patients with intrauterine growth restrictions due to placental insufficiency
2008-08-01 | E-GEOD-12216 | biostudies-arrayexpress
Project description:The Repressor Element-1 Silencing Transcription (REST) factor is a transcriptional repressor. The aim of this study is to characterize role of REST in placental influences on offspring brain. REST was ablated in mouse placenta by mating mouse carrying floxed (FL) alleles of REST with mouse that expresses Cre recombinase under the control of the promoter of placenta-specific gene Gcm1 (glial cells missing 1). To investigate placental influence on gene expression of adult offspring brain cells, single-nuclei RNA-seq was performed. Data analysis showed that ablation of placental REST significantly impacted specific pathways in choroid plexus and ependymal cells of the offspring brain.
2024-04-19 | GSE237181 | GEO
Project description:The placenta develops alongside the embryo and nurtures fetal development to term. During the first stages of embryonic development, due to low blood circulation, the blood and ambient oxygen supply is normally very low (~1-2% O2) and gradually increases upon placental invasion. While a hypoxic environment is associated with stem cell self-renewal and proliferation, persistent hypoxia may have severe effects on differentiating cells and could be the underlying cause of placental disorders. We find that human trophoblast stem cells (TSC) thrive in low oxygen, whereas differentiation of syncytiotrophoblast (STB) and extravillous trophoblast (EVT) is negatively affected by hypoxic conditions. We find that the pro-differentiation factor GCM1 (human Glial Cell Missing-1) is downregulated in low oxygen, and there is substantial reduction of GCM1-regulated genes in hypoxic conditions. Knock-out of GCM1 in TSC caused impaired EVT and STB formation and function, reduced expression of genes that respond to differentiation, and resulted in maintenance of self-renewal genes. Treatment with a PI3K inhibitor reported to reduce GCM1 protein levels likewise counteracts spontaneous or directed differentiation. Chromatin immunoprecipitation of GCM1 showed enrichment of GCM1-specific binding near key transcription factors upregulated upon differentiation including the contact inhibition factor CDKN1C. Loss of GCM1 resulted in downregulation of CDKN1C and corresponding loss of contact inhibition, implicating GCM1 in regulation of this critical process.
2024-10-02 | GSE276595 | GEO
Project description:The placenta develops alongside the embryo and nurtures fetal development to term. During the first stages of embryonic development, due to low blood circulation, the blood and ambient oxygen supply is normally very low (~1-2% O2) and gradually increases upon placental invasion. While a hypoxic environment is associated with stem cell self-renewal and proliferation, persistent hypoxia may have severe effects on differentiating cells and could be the underlying cause of placental disorders. We find that human trophoblast stem cells (TSC) thrive in low oxygen, whereas differentiation of syncytiotrophoblast (STB) and extravillous trophoblast (EVT) is negatively affected by hypoxic conditions. We find that the pro-differentiation factor GCM1 (human Glial Cell Missing-1) is downregulated in low oxygen, and there is substantial reduction of GCM1-regulated genes in hypoxic conditions. Knock-out of GCM1 in TSC caused impaired EVT and STB formation and function, reduced expression of genes that respond to differentiation, and resulted in maintenance of self-renewal genes. Treatment with a PI3K inhibitor reported to reduce GCM1 protein levels likewise counteracts spontaneous or directed differentiation. Chromatin immunoprecipitation of GCM1 showed enrichment of GCM1-specific binding near key transcription factors upregulated upon differentiation including the contact inhibition factor CDKN1C. Loss of GCM1 resulted in downregulation of CDKN1C and corresponding loss of contact inhibition, implicating GCM1 in regulation of this critical process.
2024-10-02 | GSE276594 | GEO
Project description:The placenta develops alongside the embryo and nurtures fetal development to term. During the first stages of embryonic development, due to low blood circulation, the blood and ambient oxygen supply is normally very low (~1-2% O2) and gradually increases upon placental invasion. While a hypoxic environment is associated with stem cell self-renewal and proliferation, persistent hypoxia may have severe effects on differentiating cells and could be the underlying cause of placental disorders. We find that human trophoblast stem cells (TSC) thrive in low oxygen, whereas differentiation of syncytiotrophoblast (STB) and extravillous trophoblast (EVT) is negatively affected by hypoxic conditions. We find that the pro-differentiation factor GCM1 (human Glial Cell Missing-1) is downregulated in low oxygen, and there is substantial reduction of GCM1-regulated genes in hypoxic conditions. Knock-out of GCM1 in TSC caused impaired EVT and STB formation and function, reduced expression of genes that respond to differentiation, and resulted in maintenance of self-renewal genes. Treatment with a PI3K inhibitor reported to reduce GCM1 protein levels likewise counteracts spontaneous or directed differentiation. Chromatin immunoprecipitation of GCM1 showed enrichment of GCM1-specific binding near key transcription factors upregulated upon differentiation including the contact inhibition factor CDKN1C. Loss of GCM1 resulted in downregulation of CDKN1C and corresponding loss of contact inhibition, implicating GCM1 in regulation of this critical process.
2024-10-02 | GSE276590 | GEO
Project description:The placenta develops alongside the embryo and nurtures fetal development to term. During the first stages of embryonic development, due to low blood circulation, the blood and ambient oxygen supply is normally very low (~1-2% O2) and gradually increases upon placental invasion. While a hypoxic environment is associated with stem cell self-renewal and proliferation, persistent hypoxia may have severe effects on differentiating cells and could be the underlying cause of placental disorders. We find that human trophoblast stem cells (TSC) thrive in low oxygen, whereas differentiation of syncytiotrophoblast (STB) and extravillous trophoblast (EVT) is negatively affected by hypoxic conditions. We find that the pro-differentiation factor GCM1 (human Glial Cell Missing-1) is downregulated in low oxygen, and there is substantial reduction of GCM1-regulated genes in hypoxic conditions. Knock-out of GCM1 in TSC caused impaired EVT and STB formation and function, reduced expression of genes that respond to differentiation, and resulted in maintenance of self-renewal genes. Treatment with a PI3K inhibitor reported to reduce GCM1 protein levels likewise counteracts spontaneous or directed differentiation. Chromatin immunoprecipitation of GCM1 showed enrichment of GCM1-specific binding near key transcription factors upregulated upon differentiation including the contact inhibition factor CDKN1C. Loss of GCM1 resulted in downregulation of CDKN1C and corresponding loss of contact inhibition, implicating GCM1 in regulation of this critical process.
2024-10-02 | GSE276588 | GEO
Project description:The placental microvasculature of the human fetus is essential for the efficient transfer of gases, nutrients and waste between the mother and fetus. Microvascular hypoplasia of the terminal villi is associated with the placental pathology observed in cases of severe Intra Uterine Growth Restriction (IUGR). We used novel methods to isolate a pure population of placental microvascular endothelial cells from control preterm placentas (n=3) and placenta complicated by severe IUGR (n=6) with superimposed preeclampsia (n=5). Distal placental villous tissue was collected to enrich for terminal villi. Tissue was minced, digested and placental microvascular endothelial cells (PlMEC) were positively selected using tocosylated magnetic Dynabeads labeled with Human Endothelial Antigen lectin. The purity of the PlMEC (95%) was assessed by CD31 immunocytochemistry. RNA was extracted from the PlMEC samples and also from 3 term placenta and subjected to Affymetrix microarray analysis (U133Plus2 array chips). Data from the 3 term placentas and 3 preterm PlMEC arrays was used to generate an endothelial cell specific gene profile. This profile was used to identify the endothelial genes differentially regulated in all 6 IUGR cases. BTNL9 and NTRK2 transcripts were upregulated and SAA1, GNAS and SLAMF1 transcripts were downregulated as relative to the preterm controls. These changes were validated by Real time PCR in the PlMEC samples. This novel study is the first to identify endothelial candidate genes that may play a role in the villous hypoplasia of severe IUGR. This work advances our understanding of the molecular defects in placental microvascular endothelial cells in normal and pathologic pregnancies.
2012-04-01 | GSE25861 | GEO
Project description:Maternal obesity is becoming a major health consideration for successful pregnancy outcomes. There is growing proof that maternal obesity has a negative influence on placental development and function, thereby adversely influencing offspring programming and health outcomes. However, the molecular mechanisms underlying these processes are so far poorly understood. We set out to analyse term placenta whole transcriptome in obese (n=5) and normoweight women (n=5), using Affymetrix microarray platform compromising of 50,000 probe sets. Our analysis shows that the placental transcriptome differs between normoweight and obese women. Different processes and pathways among placenta from obese women were dysregulated, including inflammation and immune responses, lipid metabolism, cell death and survival and cancer pathways, vasculogenesis and angiogenesis, and glucocorticoid receptor signaling pathway. Together, this global gene expression profiling approach demonstrates and confirms that maternal obesity creates a unique in utero environment that impairs placental transcriptome.
2017-01-07 | E-MTAB-4541 | biostudies-arrayexpress
Project description:Gene regulation is essential to placental function and fetal development. We built a genome-scale transcriptional regulatory network (TRN) of the human placenta using digital genomic footprinting and transcriptomic data. We integrated 475 transcriptomes and 12 DNase hypersensitivity datasets from placental samples to globally and quantitatively map transcription factor (TF)-target gene interactions. We performed siRNA knockdowns of 4 TFs and achieved concordance between the predicted gene targets in our TRN. This GEO dataset summarizes the results of the knockdowns for these 4 TFs: GCM1, CREB2L2, ESRRG, and GRHL2 compared to siRNA controls (SCR).
2024-07-03 | GSE245394 | GEO
Project description:Prenatal alcohol exposure (PAE) has previously been shown to alter fetal blood flow in utero and is also associated with placental insufficiency and intrauterine growth restriction (IUGR), suggesting an underlying connection between perturbed circulation and pregnancy outcomes. Here we show that a single exposure to ethanol in pregnant mice on gestational day 10 (GD10) by gavage attenuates umbilical cord blood flow transiently during gestation, explaining the observed IUGR, specifically decreased fetal weight, and morphometric indices of cranial growth. Moreover, RNAseq of the fetal portion of the placenta demonstrated that this single exposure has lasting transcriptomic changes, including upregulation of Tet3, which is associated with spontaneous abortion. Weighted gene co-expression network analysis (WGCNA) identified erythrocyte differentiation and homeostasis as important pathways associated with improved umbilical cord blood flow as gestation progresses. WGCNA also identified sensory perception of chemical stimulus/odorant and receptor activity as important pathways associated with cranial growth. Our data suggest that PAE perturbs the expression of placental genes relevant for placental hematopoiesis and environmental sensing, resulting in transient impairment of umbilical cord blood flow and subsequently, IUGR.
2022-08-16 | GSE195489 | GEO