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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

基本信息

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
项目类别：
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

项目摘要

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.

抽象的胎盘对于胎儿的健康和发育至关重要，也是孕产妇健康的潜在标志，但其状况不佳明白了。传统上，人类胎盘功能的研究主要集中在足月时获得的样本，限制了我们理解人类正常胎盘发育和功能的能力妊娠。整个怀孕期间出现的状况和疾病的发展归因于胎盘发育和随后的功能最有可能发生在妊娠早期。早期直接胎盘评估可以通过在妊娠早期末进行的绒毛膜绒毛取样（CVS）来实现。这些绒毛用于细胞遗传学检测，也是观察胎盘发育的独特窗口。我们开发了储存未使用的绒毛的技术，用于后续的多组学测试，包括基因组学，表观基因组学和转录组学，并从这些妊娠中收集足月胎盘样本，提供了解胎盘发育和整个妊娠期潜在功能的窗口。最近，我们确定了性别妊娠早期常染色体和性染色体上表达的许多基因存在差异胎盘与足月时发现的胎盘不同，表明胎盘发育存在性别差异早在妊娠的前三个月。此外，我们还发现了非编码 RNA 部分的差异性别，由常染色体和性染色体表达。因为这些非编码 RNA 很重要转录活性和整体功能的调节因子，它们可以解释更微妙的性别由于胎盘发育而在胎儿发育和疾病中观察到的差异。然而，性尚未在正常胎盘中研究通过非编码 RNA 进行基因调控的二态性发展。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，我们有有机会更好地了解这些非编码 RNA 对胎盘 RNA 调节的作用两性在整个妊娠期的发育。此外，我们还有相应的母婴银行来自妊娠的血浆，其中储存有绒毛。我们最近从储存的胎盘 RNA 中分离出来样本并打算使用这些样本来识别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妊娠早期和足月胎盘样本以确定总 RNA（非编码和编码）的正常且性别不同的胎盘特征整个妊娠期。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出可在母体循环中识别的功能相关特征。