Noncoding RNA regulation of the human placental transcriptome among the sexes

性别中人胎盘转录组的非编码RNA调控

• 批准号: 9308742
• 负责人: Margareta Pisarska
• 金额: $ 45万
• 依托单位: CEDARS-SINAI MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-03-10 至 2019-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9308742
• 关键词: Affect; Apoptosis; Bioinformatics; Blood Circulation; Chorion; Chorionic villi; Code; Cytogenetic Analysis; Development; Diagnostic tests; Disease; Female; Fetal Development; Fetal Diseases; Fetus; First Pregnancy Trimester; Freezing; Future; Gene Expression; Gene Expression Regulation; Genes; Genetic; Genetic Transcription; Genomics; Goals; Health; Human; Individual; Lead; Maternal Health; Modernization; Molecular; Organ; Placenta; Placentation; Plasma; Pregnancy; Primigravidities; RNA; Regulation; Role; Sampling; Sex Characteristics; Sex Chromosomes; Source; Statistical Methods; Techniques; Technology; Testing; Third Pregnancy Trimester; Untranslated RNA; Villus; autosome; biobank; cell motility; differential expression; epigenomics; fetal; in utero; male; multiple omics; sex; sexual dimorphism; transcriptome; transcriptome sequencing; transcriptomics; trophoblast

Abstract The placenta, critical for fetal health and development and a potential marker of maternal health, is poorly understood. Traditionally, studies of human placental function have focused on samples obtained at term, limiting our ability to understand both normal placental development and function throughout human gestation. The development of conditions and diseases which manifest throughout pregnancy attributed to placental development and subsequently function most likely occur early in gestation. Early direct placental assessment can be achieved through chorionic villus sampling (CVS), performed in the late first trimester. These villi, used for cytogenetic testing, also represent a unique window into the developing placenta. We developed techniques to bank unused villi for use in subsequent multiple –omics testing including genomics, epigenomics and transcriptomics and also collect term placental samples from these pregnancies providing a window into placental development and potential function throughout gestation. Recently, we identified sex differences in a number of genes expressed on autosomes and sex chromosomes in the first trimester placenta, unique from those identified at term, suggesting there are sex differences in placental development as early as the first trimester. In addition, we also identified differences in noncoding RNA fractions among the sexes, expressed from both autosomes and sex chromosomes. As these noncoding RNA’s are important regulators of transcriptional activity and hence overall function, they may explain the more subtle sex differences observed in fetal development and disease as a result of placental development. However, sexual dimorphism of gene regulation through noncoding RNA has not been studied in normal placental development. Thus, using our already stored samples and our genomics bioinformatics expertise, we have the opportunity to better understand the role of these noncoding RNAs on RNA regulation in placental development throughout gestation among the sexes. In addition, we have corresponding banked maternal plasma from pregnancies in which villi are banked. We have recently isolated placental RNA from our stored samples and intend to use these samples to identify key markers of placental function that are reflective of the intrauterine placenta. Thus, we intend to use our established banked first trimester and term placental samples to establish a normative and sexually distinct placental signature of total RNA (noncoding and coding) throughout gestation. We also intend to identify functional activity of noncoding RNAs on placental function followed by the development of a functionally relevant signature that can be identified in the maternal circulation.

摘要 胎盘对胎儿的健康和发育至关重要，也是母体健康的潜在标志，但胎盘的状况很差。 明白了。传统上，对人类胎盘功能的研究主要集中在足月采集的样本上， 限制了我们理解人类正常胎盘发育和功能的能力 怀孕了。疾病在整个怀孕期间表现出来的状况和疾病的发展，归因于 胎盘发育和随后的功能很可能发生在妊娠早期。早期直接胎盘 评估可以通过绒毛取样(CVS)来实现，在妊娠早期后期进行。 这些绒毛用于细胞遗传学测试，也是了解发育中的胎盘的独特窗口。我们 开发了储存未使用的绒毛以用于随后的包括基因组学在内的多重组学测试的技术， 表观基因组学和转录组学，还收集这些妊娠的足月胎盘样本，提供 了解整个孕期胎盘发育和潜在功能的窗口。最近，我们确认了性别 妊娠早期常染色体和性染色体上多个基因表达的差异 胎盘，与足月鉴定的胎盘不同，表明胎盘发育存在性别差异 早在怀孕的前三个月。此外，我们还确定了非编码RNA组分的差异 性别，在常染色体和性染色体上都表达。因为这些非编码的RNA很重要 转录活动和整体功能的调节，它们可以解释更微妙的性别 观察到胎盘发育导致的胎儿发育和疾病的差异。然而，性 在正常胎盘中，还没有研究过非编码RNA对基因调控的二型性 发展。因此，利用我们已经存储的样本和我们的基因组生物信息学专业知识，我们拥有 更好地了解这些非编码RNA在胎盘RNA调控中的作用的机会 在整个孕期两性之间的发育。此外，我们有相应的母体银行 绒毛储存的妊娠所产生的血浆。我们最近从我们的储存中提取了胎盘RNA 并打算使用这些样本来确定反映胎盘功能的关键标志物 宫内胎盘。因此，我们打算使用我们已建立的早孕期和胎盘期。 样本以建立总RNA的标准化和性别差异的胎盘签名(非编码和编码) 在整个怀孕过程中。我们还打算鉴定非编码RNA对胎盘功能的功能活性。 随后开发了可在母体循环中识别的功能相关的签名。