Trophoblast-Guided Uterine Transformation in the Establishment of Pregnancy
滋养细胞引导子宫转化以建立妊娠
基本信息
- 批准号:10446395
- 负责人:
- 金额:$ 46.09万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-05-15 至 2027-02-28
- 项目状态:未结题
- 来源:
- 关键词:Abruptio PlacentaeCell CommunicationCell LineageCellsChromatinDevelopmentDevelopmental ProcessDiagnosticDiseaseEarly DiagnosisEmbryoEndothelial CellsEnvironmentEtiologyEventFailureFetal Growth RetardationFunctional disorderGoalsHealthHumanImmuneInfiltrationModelingMolecularPathogenesisPathway interactionsPlacentaPlacentationPopulationPre-EclampsiaPregnancyPremature BirthProcessPropertyRattusResearch Project GrantsRoleSiteSmooth Muscle MyocytesStromal CellsTherapeutic InterventionUterusearly pregnancy lossgenetic manipulationgenome-wide analysisloss of functionobstetrical syndromespostnatalpregnancy disordertargeted treatmenttranscriptometrophoblasttrophoblast stem cell
项目摘要
PROJECT SUMMARY/ABSTRACT
Trophoblast cell derivatives of the embryo contribute to restructuring the uterine environment, an event
required for the establishment of a successful pregnancy. The rat and human each possess a uterine-
placental interface that is characterized by deep intrauterine infiltration of trophoblast cells, which contribute to
dynamic changes in uterine immune cell, endothelial cell, smooth muscle cell, and stromal cell constituents.
This important developmental process is directed by specialized trophoblast cells possessing invasive
properties with the potential of targeting maternal cells within the uterine compartment. In the human, these
invasive trophoblast cells are referred to as extravillous trophoblast (EVT). Disruptions in differentiation of the
invasive trophoblast/EVT cell lineage, intrauterine trophoblast cell invasion, and/or trophoblast cell-directed
uterine cell modulation contribute to early pregnancy loss, placental dysfunction, pregnancy-related diseases,
and a range of postnatal health issues. The project focuses on placenta specific 1 (PLAC1), an intrinsic
regulator of placentation. Our long-term goal is to elucidate regulatory processes controlling development of
the invasive trophoblast/EVT cell lineage and its role in establishing the uterine-placental interface. In this
project, our efforts are focused on two aims. In Aim 1, we dissect the actions of PLAC1 in the establishment of
the invasive trophoblast cell lineage. In Aim 2 we investigate trophoblast cell-uterine cell crosstalk and
plasticity at the uterine-placental interface. Experimentation utilizes genetically manipulated loss-of-function rat
models, trophoblast stem cells, and genome-wide analyses of transcriptomes and chromatin landscapes.
Execution of this research project will facilitate elucidation of molecular pathways controlling trophoblast-guided
transformation of the uterine environment and will create a platform for understanding the pathogenesis of
early pregnancy loss and placental anomalies leading to pregnancy disorders.
项目总结/摘要
胚胎的滋养层细胞衍生物有助于重组子宫环境,这是一个事件
这是成功怀孕所必需的。老鼠和人类都有子宫
胎盘界面,其特征在于滋养层细胞的子宫内深层浸润,这有助于
子宫免疫细胞、内皮细胞、平滑肌细胞和基质细胞成分的动态变化。
这一重要的发育过程是由具有侵袭性的特化滋养层细胞指导的。
具有靶向子宫隔室内的母体细胞的潜力的性质。在人类中,这些
侵袭性滋养层细胞被称为绒毛外滋养层(EVT)。分化障碍,
侵袭性滋养层/EVT细胞谱系、子宫内滋养层细胞侵袭和/或滋养层细胞定向的
子宫细胞调节导致早孕丢失、胎盘功能障碍、妊娠相关疾病,
以及一系列产后健康问题。该项目的重点是胎盘特异性1(PLAC 1),一种内在的
胎座形成的调节器。我们的长期目标是阐明控制发展的调控过程,
侵袭性滋养层/EVT细胞谱系及其在建立子宫-胎盘界面中的作用。在这
项目,我们的努力集中在两个目标。在目的1中,我们剖析了PLAC 1在建立
侵入性滋养层细胞谱系。在目标2中,我们研究滋养层细胞-子宫细胞串扰,
子宫-胎盘界面的可塑性。实验利用基因操纵的功能丧失大鼠
模型、滋养层干细胞以及转录组和染色质景观的全基因组分析。
该研究项目的实施将有助于阐明控制滋养层细胞引导的细胞凋亡的分子途径。
子宫环境的改变,并将为了解子宫内膜异位症的发病机制创造一个平台。
早期流产和胎盘异常导致妊娠障碍。
项目成果
期刊论文数量(0)
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会议论文数量(0)
专利数量(0)
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MICHAEL J SOARES的其他文献
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{{ truncateString('MICHAEL J SOARES', 18)}}的其他基金
Trophoblast-Guided Uterine Transformation in the Establishment of Pregnancy
滋养细胞引导子宫转化以建立妊娠
- 批准号:
10622609 - 财政年份:2022
- 资助金额:
$ 46.09万 - 项目类别:
Trophoblast-Uterine Cell Dynamics at the Maternal-Fetal Interface
母胎界面的滋养层-子宫细胞动力学
- 批准号:
10271279 - 财政年份:2020
- 资助金额:
$ 46.09万 - 项目类别:
RESEARCH PROJECT III: Histone H3K9 Methylation and Trophoblast Lineage Developmen
研究项目 III:组蛋白 H3K9 甲基化和滋养层谱系发育
- 批准号:
9341564 - 财政年份:2016
- 资助金额:
$ 46.09万 - 项目类别:
Natural Killer Cells and Hemochorial Placentation
自然杀伤细胞和血绒质胎盘着床
- 批准号:
8810079 - 财政年份:2015
- 资助金额:
$ 46.09万 - 项目类别:
Natural Killer Cells and Hemochorial Placentation
自然杀伤细胞和血绒质胎盘着床
- 批准号:
9036420 - 财政年份:2015
- 资助金额:
$ 46.09万 - 项目类别:
Stem Cells and Epigenetics of Trophoblast Lineage Development
滋养层谱系发育的干细胞和表观遗传学
- 批准号:
8897425 - 财政年份:2014
- 资助金额:
$ 46.09万 - 项目类别:
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