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Fetal transcriptome

Marion Rouzaire, Aurélie Comptour, Corinne Belville, Damien Bouvier, Gaël Clairefond, Flora Ponelle, Vincent Sapin, Denis Gallot, Loïc Blanchon
Thirty percent of preterm births directly result from preterm premature rupture of fetal membranes (PPROM). Clinical management currently proposes using a collagen plug to mechanically stop loss of amniotic fluid. Vitamin A and its active metabolite (retinoic acid) have well-known pro-healing properties and could thus make good candidates as a proposable adjuvant to this mechanical approach. Here we investigate the molecular mechanisms involved in the pro-healing properties of all-trans retinoic acid (atRA) in fetal membranes via an approach using an in vitro primary amniocyte wound model and transcriptomics...
October 18, 2016: International Journal of Biochemistry & Cell Biology
Carmela Nardelli, Ilaria Granata, Laura Iaffaldano, Valeria D'Argenio, Valentina Del Monaco, Giuseppe Maria Maruotti, Daniela Omodei, Luigi Del Vecchio, Pasquale Martinelli, Francesco Salvatore, Mario Rosario Guarracino, Lucia Sacchetti, Lucio Pastore
Clinical findings and data obtained in animal models indicate that nutrient uptake and exposure to environmental agents during pregnancy may affect fetal/newborn gestational programming thereby resulting in obesity and/or obesity-related disorders in offspring. Human amniotic mesenchymal stem cells (hA-MSCs) differentiate into adipocytes, and are thus a suitable model to investigate adipocyte functions in obesity. The aim of this study was to elucidate the miRNome of hA-MSCs and its contribution to obesity in pregnancy...
October 20, 2016: Stem Cells and Development
Jimena Giudice, Zheng Xia, Wei Li, Thomas A Cooper
The RNA binding protein Celf1 regulates alternative splicing in the nucleus and mRNA stability and translation in the cytoplasm. Celf1 is strongly down-regulated during mouse postnatal heart development. Its re-induction in adults induced severe heart failure and reversion to fetal splicing and gene expression patterns. However, the impact of Celf1 depletion on cardiac transcriptional and posttranscriptional dynamics in neonates has not been addressed. We found that homozygous Celf1 knock-out neonates exhibited cardiac dysfunction not observed in older homozygous animals, although homozygous mice are smaller than wild type littermates throughout development...
October 19, 2016: Scientific Reports
Andreas Schlitzer, Joachim L Schultze
Tissue macrophages of fetal and adult origin have pivotal roles in tissue homeostasis and organ inflammation. Recently several functional and transcriptomic studies have revealed their unique module-like transcriptomic organization leading to enormous tissue-dependent functional plasticity. In this review, we discuss the development, tissue adaption and function of resident murine and human macrophages. Finally, we discuss our limited knowledge on human tissue macrophages and provide our opinion on their relevance during disease and for clinical application...
October 18, 2016: Immunology and Cell Biology
Jing-Woei Li, Heung-Man Lee, Ying Wang, Amy Hin-Yan Tong, Kevin Y Yip, Stephen Kwok-Wing Tsui, Si Lok, Risa Ozaki, Andrea O Luk, Alice P S Kong, Wing-Yee So, Ronald C W Ma, Juliana C N Chan, Ting-Fung Chan
Protein interactions play significant roles in complex diseases. We analyzed peripheral blood mononuclear cells (PBMC) transcriptome using a multi-method strategy. We constructed a tissue-specific interactome (T2Di) and identified 420 molecular signatures associated with T2D-related comorbidity and symptoms, mainly implicated in inflammation, adipogenesis, protein phosphorylation and hormonal secretion. Apart from explaining the residual associations within the DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) study, the T2Di signatures were enriched in pathogenic cell type-specific regulatory elements related to fetal development, immunity and expression quantitative trait loci (eQTL)...
October 18, 2016: Scientific Reports
Clare L Whitehead, Susan P Walker, Stephen Tong
Circulating nucleic acids have revolutionized prenatal diagnosis in the last decade, allowing non-invasive screening for single gene or chromosomal defects using a single sample of maternal blood. In addition to deoxyribonucleic acids (DNA), ribonucleic acids (RNA) from the placenta are released into the maternal blood from early in pregnancy and may reflect changes in gene expression occurring within the placenta. Measuring circulating RNA may therefore provide insights into the placental transcriptome without the need for invasive testing...
October 6, 2016: Prenatal Diagnosis
Amal Al-Garawi, Vincent J Carey, Divya Chhabra, Hooman Mirzakhani, Jarrett Morrow, Jessica Lasky-Su, Weiliang Qiu, Nancy Laranjo, Augusto A Litonjua, Scott T Weiss
BACKGROUND: Patterns of gene expression of human pregnancy are poorly understood. In a trial of vitamin D supplementation in pregnant women, peripheral blood transcriptomes were measured longitudinally on 30 women and used to characterize gene co-expression networks. OBJECTIVE: Studies suggest that increased maternal Vitamin D levels may reduce the risk of asthma in early life, yet the underlying mechanisms have not been examined. In this study, we used a network-based approach to examine changes in gene expression profiles during the course of normal pregnancy and evaluated their association with maternal Vitamin D levels...
2016: PloS One
Aline Rideau Batista Novais, Hoa Pham, Yohan Van de Looij, Miguel Bernal, Jerome Mairesse, Elodie Zana-Taieb, Marina Colella, Pierre-Henri Jarreau, Julien Pansiot, Florent Dumont, Stéphane Sizonenko, Pierre Gressens, Christiane Charriaut-Marlangue, Mickael Tanter, Charlie Demene, Daniel Vaiman, Olivier Baud
Fetal growth restriction (FGR) is a major complication of human pregnancy, frequently resulting from placental vascular diseases and prenatal malnutrition, and is associated with adverse neurocognitive outcomes throughout life. However, the mechanisms linking poor fetal growth and neurocognitive impairment are unclear. Here, we aimed to correlate changes in gene expression induced by FGR in rats and abnormal cerebral white matter maturation, brain microstructure, and cortical connectivity in vivo. We investigated a model of FGR induced by low-protein-diet malnutrition between embryonic day 0 and birth using an interdisciplinary approach combining advanced brain imaging, in vivo connectivity, microarray analysis of sorted oligodendroglial and microglial cells and histology...
December 2016: Glia
Yi Young Kim, Ivan Roubal, Youn Soo Lee, Jin Seok Kim, Michael Hoang, Nathan Mathiyakom, Yong Kim
Adverse effect of alcohol on neural function has been well documented. Especially, the teratogenic effect of alcohol on neurodevelopment during embryogenesis has been demonstrated in various models, which could be a pathologic basis for fetal alcohol spectrum disorders (FASDs). While the developmental defects from alcohol abuse during gestation have been described, the specific mechanisms by which alcohol mediates these injuries have yet to be determined. Recent studies have shown that alcohol has significant effect on molecular and cellular regulatory mechanisms in embryonic stem cell (ESC) differentiation including genes involved in neural development...
2016: PloS One
Florian Finkernagel, Silke Reinartz, Sonja Lieber, Till Adhikary, Annika Wortmann, Nathalie Hoffmann, Tim Bieringer, Andrea Nist, Thorsten Stiewe, Julia M Jansen, Uwe Wagner, Sabine Müller-Brüsselbach, Rolf Müller
Macrophages occur as resident cells of fetal origin or as infiltrating blood monocyte-derived cells. Despite the critical role of tumor-associated macrophages (TAMs) in tumor progression, the contribution of these developmentally and functionally distinct macrophage subsets and their alteration by the tumor microenvironment are poorly understood. We have addressed this question by comparing TAMs from human ovarian carcinoma ascites, resident peritoneal macrophages (pMPHs) and monocyte-derived macrophages (MDMs)...
September 21, 2016: Oncotarget
Lillian M Zwemer, Sarah L Nolin, Patricia M Okamoto, Marcia Eisenberg, Heather C Wick, Diana W Bianchi
OBJECTIVE: We tested the hypothesis that FMR1 expansions would result in global gene dysregulation as early as the second trimester of human fetal development. METHOD: Using cell-free fetal RNA obtained from amniotic fluid supernatant and expression microarrays we compared RNA levels in samples from fetuses with premutation or full mutation allele expansions to control samples. RESULTS: We found clear signals of differential gene expression relating to a variety of cellular functions, including ubiquitination, mitochondrial function and neuronal/synaptic architecture, among others...
September 20, 2016: Prenatal Diagnosis
Peck Yean Tan, Cheng Wei Chang, Kaibo Duan, Michael Poidinger, Kai Lyn Ng, Yap Seng Chong, Peter D Gluckman, Walter Stünkel
Wharton's jelly-derived Mesenchymal Stem Cells (MSCs) isolated from newborns with intrauterine fetal growth restriction were previously shown to exert anabolic features including insulin hypersensitivity. Here, we extend these observations and demonstrate that MSCs from small for gestational age (SGA) individuals have decreased mitochondrial oxygen consumption rates. Comparing normally grown and SGA MSCs using next generation sequencing studies, we measured global transcriptomic and epigenetic profiles and identified E2F1 as an over-expressed transcription factor regulating oxidative metabolism in the SGA group...
2016: PloS One
Elizabeth P Crowe, Ferit Tuzer, Brian D Gregory, Greg Donahue, Sager J Gosai, Justin Cohen, Yuk Y Leung, Emre Yetkin, Raffaella Nativio, Li-San Wang, Christian Sell, Nancy M Bonini, Shelley L Berger, F Brad Johnson, Claudio Torres
Aging is a major risk factor for many neurodegenerative disorders. A key feature of aging biology that may underlie these diseases is cellular senescence. Senescent cells accumulate in tissues with age, undergo widespread changes in gene expression, and typically demonstrate altered, pro-inflammatory profiles. Astrocyte senescence has been implicated in neurodegenerative disease, and to better understand senescence-associated changes in astrocytes, we investigated changes in their transcriptome using RNA sequencing...
2016: Frontiers in Aging Neuroscience
Valentina Medici, Dorothy A Kieffer, Noreene M Shibata, Harpreet Chima, Kyoungmi Kim, Angela Canovas, Juan F Medrano, Alma D Islas-Trejo, Kusum K Kharbanda, Kristin Olson, Ruijun J Su, Mohammad S Islam, Raisa Syed, Carl L Keen, Amy Y Miller, John C Rutledge, Charles H Halsted, Janine M LaSalle
Wilson disease (WD), a genetic disorder affecting copper transport, is characterized by hepatic and neurological manifestations with variable and often unpredictable presentation. Global DNA methylation in liver was previously modified by dietary choline in tx-j mice, a spontaneous mutant model of WD. We therefore hypothesized that the WD phenotype and hepatic gene expression of tx-j offspring could be modified by maternal methyl supplementation during pregnancy. In an initial experiment, female tx-j mice or wild type mice were fed control or choline-supplemented diets two weeks prior to mating through embryonic day 17...
September 9, 2016: Epigenetics: Official Journal of the DNA Methylation Society
Quan Wu, Kurumi Fukuda, Yuzuru Kato, Zhi Zhou, Chu-Xia Deng, Yumiko Saga
The differential programming of sperm and eggs in gonads is a fundamental topic in reproductive biology. Although the sexual fate of germ cells is believed to be determined by signaling factors from sexually differentiated somatic cells in fetal gonads, the molecular mechanism that determines germ cell fate is poorly understood. Herein, we show that mothers against decapentaplegic homolog 4 (SMAD4) in germ cells is required for female-type differentiation. Germ cells in Smad4-deficient ovaries respond to retinoic acid signaling but fail to undergo meiotic prophase I, which coincides with the weaker expression of genes required for follicular formation, indicating that SMAD4 signaling is essential for oocyte differentiation and meiotic progression...
September 2016: PLoS Biology
Li Zhang, Bin Wang, Ling Li, Dong-Meng Qian, Hong Yu, Mei-Lan Xue, Ming Hu, Xu-Xia Song
The prominent feature of human cytomegalovirus (HCMV) is cell tropism specificity for human fetal nervous system, which leads to severe fetal nervous system damage especially in first-trimester gestation. In this study, human astrocytes isolated from fetal brain were infected with HCMV AD169 and whole genome transcriptome profile was performed. The results showed that the gene expression of interferon stimulated genes (ISGs), chemokine and chemokine receptors were significantly up-regulated (P < 0.01)...
September 2, 2016: Journal of Medical Virology
Faycal Guedj, Jeroen LA Pennings, Lauren J Massingham, Heather C Wick, Ashley E Siegel, Umadevi Tantravahi, Diana W Bianchi
Anatomical and functional brain abnormalities begin during fetal life in Down syndrome (DS). We hypothesize that novel prenatal treatments can be identified by targeting signaling pathways that are consistently perturbed in cell types/tissues obtained from human fetuses with DS and mouse embryos. We analyzed transcriptome data from fetuses with trisomy 21, age and sex-matched euploid controls, and embryonic day 15.5 forebrains from Ts1Cje, Ts65Dn, and Dp16 mice. The new datasets were compared to other publicly available datasets from humans with DS...
2016: Scientific Reports
Encarnacion Montecino-Rodriguez, Michael Fice, David Casero, Beata Berent-Maoz, Chad L Barber, Kenneth Dorshkind
B cell development is often depicted as a linear process initiating in the fetus and continuing postnatally. Using a PU.1 hypomorphic mouse model, we found that B-1 and B-2 lymphopoiesis occurred in distinct fetal and adult waves differentially dependent on the Sfpi1 14 kB upstream regulatory element. The initial wave of fetal B-1 development was absent in PU.1 hypomorphic mice, while subsequent fetal and adult waves emerged. In contrast, B-2 lymphopoiesis occurred in distinct fetal and adult waves. Whole-transcriptome profiling of fetal and adult B cell progenitors supported the existence of three waves of B-1 and two waves of B-2 development and revealed that the network of transcription factors governing B lineage specification and commitment was highly divergent between B-1 and B-2 progenitors...
September 20, 2016: Immunity
Andrew E Teschendorff, Shijie C Zheng, Andy Feber, Zhen Yang, Stephan Beck, Martin Widschwendter
BACKGROUND: Hypermethylation of transcription factor promoters bivalently marked in stem cells is a cancer hallmark. However, the biological significance of this observation for carcinogenesis is unclear given that most of these transcription factors are not expressed in any given normal tissue. METHODS: We analysed the dynamics of gene expression between human embryonic stem cells, fetal and adult normal tissue, as well as six different matching cancer types. In addition, we performed an integrative multi-omic analysis of matched DNA methylation, copy number, mutational and transcriptomic data for these six cancer types...
2016: Genome Medicine
Andrej Fabrizius, Daniel Andre, Tilmann Laufs, Anne Bicker, Stefan Reuss, Elena Porto, Thorsten Burmester, Thomas Hankeln
Neuroglobin (Ngb) is a respiratory protein that is almost exclusively expressed in the vertebrate nervous system. Despite many years of research, the exact function and even the expression sites of Ngb are still a matter of debate. However, to investigate hypotheses surrounding the potential roles of Ngb, a detailed knowledge of its major and minor expression sites is indispensable. We have therefore evaluated Ngb expression by extensive bioinformatic analysis using publicly available transcriptome data (RNA-Seq)...
August 16, 2016: Neuroscience
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