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Comparative analysis of mouse and human placentae across gestation reveals species-specific regulators of placental development

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE100053 | GEO | 2018/02/15

REPOSITORIES: GEO

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Comparative analysis of mouse and human placentae across gestation reveals species-specific regulators of placental development.

Project description:An increasing body of evidence points to significant spatio-temporal differences in early placental development between mouse and human, but a detailed comparison of placentae in these two species is missing. We set out to compare placentae from both species across gestation, with a focus on trophoblast progenitor markers. We found that CDX2 and ELF5, but not EOMES, are expressed in early post-implantation trophoblast subpopulations in both species. Genome-wide expression profiling of mouse and human placentae revealed clusters of genes with distinct co-expression patterns across gestation. Overall, there was a closer fit between patterns observed in the placentae when the inter-species comparison was restricted to human placentae through gestational week 16 (thus, excluding full-term samples), suggesting that the developmental timeline in mouse runs parallel to the first half of human placental development. In addition, we identified VGLL1 as a human-specific marker of proliferative cytotrophoblast, where it is co-expressed with the transcription factor TEAD4. As TEAD4 is involved in trophectoderm specification in the mouse, we posit a regulatory role for VGLL1 in early events during human placental development.

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Comparative analysis of mouse and human placentae across gestation reveals species-specific regulators of placental development [mouse]

Project description:In this study, we compared the genome-wide transcriptome of mouse and human placentas across gestation to identify species-specific signatures of early development. We also compared human placental signatures to purified primary cytotrophoblasts (CTB) isolated from placentae at different gestational age.

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Comparative analysis of mouse and human placentae across gestation reveals species-specific regulators of placental development [Primary CTB]

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Comparative analysis of mouse and human placentas across gestation reveals species-specific regulators of placental development [human]

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Comparative analysis of mouse and human placentae across gestation reveals species-specific regulators of placental development

Project description:Comparative analysis of mouse and human placentae across gestation reveals species-specific regulators of placental development

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Comparative analysis of mouse and human placentae across gestation reveals species-specific regulators of placental development [Primary CTB]

Project description:Comparative analysis of mouse and human placentae across gestation reveals species-specific regulators of placental development [Primary CTB]

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Placental Metabolomics for Assessment of Sex-specific Differences in Fetal Development During Normal Gestation.

Project description:The placenta is a metabolically active interfacial organ that plays crucial roles in fetal nutrient delivery, gas exchange and waste removal reflecting dynamic maternal and fetal interactions during gestation. There is growing evidence that the sex of the placenta influences fetal responses to external stimuli in utero, such as changes in maternal nutrition and exposure to environmental stressors. However, the exact biochemical mechanisms associated with sex-specific metabolic adaptations during pregnancy and its link to placental function and fetal development remain poorly understood. Herein, multisegment injection-capillary electrophoresis-mass spectrometry is used as a high throughput metabolomics platform to characterize lyophilized placental tissue (~2?mg dried weight) from C57BL/6J mice fed a standardized diet. Over 130 authentic metabolites were consistently measured from placental extracts when using a nontargeted metabolomics workflow with stringent quality control and robust batch correction. Our work revealed distinct metabolic phenotype differences that exist between male (n?=?14) and female (n?=?14) placentae collected at embryonic day E18.5. Intracellular metabolites associated with fatty acid oxidation and purine degradation were found to be elevated in females as compared to male placentae (p?<?0.05, effect size >0.40), including uric acid, valerylcarnitine, hexanoylcarnitine, and 3-hydroxyhexanolycarnitine. This murine model sheds new insights into sex-specific differences in placental mitochondrial function and protective mechanisms against deleterious oxidative stress that may impact fetal growth and birth outcomes later in life.

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Comparative Analysis of the Transcriptome and Proteome during Mouse Placental Development.

Project description:The condition of the placenta is a determinant of the short- and long-term health of the mother and the fetus. However, critical processes occurring in early placental development, such as trophoblast invasion and establishment of placental metabolism, remain poorly understood. To gain a better understanding of the genes involved in regulating these processes, we utilized a multiomics approach, incorporating transcriptome, proteome, and phosphoproteome data generated from mouse placental tissue collected at two critical developmental time points. We found that incorporating information from both the transcriptome and proteome identifies genes associated with time point-specific biological processes, unlike using the proteome alone. We further inferred genes upregulated on the basis of the proteome data but not the transcriptome data at each time point, leading us to identify 27 genes that we predict to have a role in trophoblast migration or placental metabolism. Finally, using the phosphoproteome data set, we discovered novel phosphosites that may play crucial roles in the regulation of placental transcription factors. By generating the largest proteome and phosphoproteome data sets in the developing placenta, and integrating transcriptome analysis, we uncovered novel aspects of placental gene regulation.

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Project description:Mammalian development in utero is absolutely dependent on proper placental development, which is ultimately regulated by the placental genome. The regulation of the placental genome can be directly studied by exploring the underlying organisation of the placental transcriptome through a systematic analysis of gene-wise co-expression relationships.In this study, we performed a comprehensive analysis of human placental co-expression using RNA sequencing and intergrated multiple transcriptome datasets spanning human gestation. We identified modules of co-expressed genes that are preserved across human gestation, and also identifed modules conserved in the mouse indicating conserved molecular networks involved in placental development and gene expression patterns more specific to late gestation. Analysis of co-expressed gene flanking sequences indicated that conserved co-expression modules in the placenta are regulated by a core set of transcription factors, including ZNF423 and EBF1. Additionally, we identified a gene co-expression module enriched for genes implicated in the pregnancy pathology preeclampsia. By using an independnet transcriptome dataset, we show that these co-expressed genes are differentially expressed in preeclampsia.This study represents a comprehensive characterisation of placental co-expression and provides insight into potential transcriptional regulators that govern conserved molecular programs fundamental to placental development.

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Comparative Characterization of Cardiac Development Specific microRNAs: Fetal Regulators for Future.

Project description:MicroRNAs (miRNAs) are small, conserved RNAs known to regulate several biological processes by influencing gene expression in eukaryotes. The implication of miRNAs as another player of regulatory layers during heart development and diseases has recently been explored. However, there is no study which elucidates the profiling of miRNAs during development of heart till date. Very limited miRNAs have been reported to date in cardiac context. In addition, integration of large scale experimental data with computational and comparative approaches remains an unsolved challenge.The present study was designed to identify the microRNAs implicated in heart development using next generation sequencing, bioinformatics and experimental approaches. We sequenced six small RNA libraries prepared from different developmental stages of the heart using chicken as a model system to produce millions of short sequence reads. We detected 353 known and 703 novel miRNAs involved in heart development. Out of total 1056 microRNAs identified, 32.7% of total dataset of known microRNAs displayed differential expression whereas seven well studied microRNAs namely let-7, miR-140, miR-181, miR-30, miR-205, miR-103 and miR-22 were found to be conserved throughout the heart development. The 3'UTR sequences of genes were screened from Gallus gallus genome for potential microRNA targets. The target mRNAs were appeared to be enriched with genes related to cell cycle, apoptosis, signaling pathways, extracellular remodeling, metabolism, chromatin remodeling and transcriptional regulators. Our study presents the first comprehensive overview of microRNA profiling during heart development and prediction of possible cardiac specific targets and has a big potential in future to develop microRNA based therapeutics against cardiac pathologies where fetal gene re-expression is witnessed in adult heart.

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