Analysis of environmentally-sensitive epigenetic machinery during osteogenic differentiation

成骨分化过程中环境敏感的表观遗传机制分析

基本信息

批准号：
10746311
负责人：
Nicole Renee Sparks
金额：
$ 4.55万
依托单位：
UNIVERSITY OF CALIFORNIA-IRVINE
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-05-11 至 2025-08-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10746311
关键词：
Adult Affect Air Air Pollutants Air Pollution Area Back Bioinformatics Bone Development Bone Injury Calcium Cardiovascular Diseases Chemicals Chronic Cities Communities Congenital Abnormality County Data Defect Deposition Development Embryo Endocrine Disruptors Environment Environmental Health Environmental Pollutants Epigenetic Process Exclusion Experimental Designs Exposure to Future Gases Genetic Predisposition to Disease Health Human Image Incidence Industrialization Infant Injury Knowledge Link Los Angeles Malignant Neoplasms Mass Fragmentography Medial Mediating MicroRNAs Molecular Molecular Toxicology Natural Disasters Natural Increases Osteoblasts Osteogenesis Outcome Participant Particulate Matter Phenotype Policies Pollution Population Density Positioning Attribute Quality Control Reporting Respiratory Disease Risk Risk Factors Sampling Scanning Science Skeletal Development Skeletal system Source Stains System Testing Time Tobacco smoke Toxic Environmental Substances Toxicant exposure Toxicology Transcriptional Regulation Vulnerable Populations Work adverse birth outcomes air sampling aqueous bone checkup examination developmental toxicology exhaust follow-up forest human embryonic stem cell in utero in vitro Model insight interest low socioeconomic status mRNA Expression marginalized community miRNA expression profiling mineralization novel osteogenic parent grant pollutant prenatal prenatal exposure reproductive response skeletal toxicant

Adult Affect Air Air Pollutants Air Pollution Area Back Bioinformatics Bone Development Bone Injury Calcium Cardiovascular Diseases Chemicals Chronic Cities Communities Congenital Abnormality County Data Defect Deposition Development Embryo Endocrine Disruptors Environment Environmental Health Environmental Pollutants Epigenetic Process Exclusion Experimental Designs Exposure to Future Gases Genetic Predisposition to Disease Health Human Image Incidence Industrialization Infant Injury Knowledge Link Los Angeles Malignant Neoplasms Mass Fragmentography Medial Mediating MicroRNAs Molecular Molecular Toxicology Natural Disasters Natural Increases Osteoblasts Osteogenesis Outcome Participant Particulate Matter Phenotype Policies Pollution Population Density Positioning Attribute Quality Control Reporting Respiratory Disease Risk Risk Factors Sampling Scanning Science Skeletal Development Skeletal system Source Stains System Testing Time Tobacco smoke Toxic Environmental Substances Toxicant exposure Toxicology Transcriptional Regulation Vulnerable Populations Work adverse birth outcomes air sampling aqueous bone checkup examination developmental toxicology exhaust follow-up forest human embryonic stem cell in utero in vitro Model insight interest low socioeconomic status mRNA Expression marginalized community miRNA expression profiling mineralization novel osteogenic parent grant pollutant prenatal prenatal exposure reproductive response skeletal toxicant

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项目摘要

PROJECT ABSTRACT Impacts of health-related issues are considered proportional to areas with dense air pollution. Air pollution composition is based highly on the area of pollution, however, are made up by general pollutants such as gases from exhaust, particulate matter, and compounds released from burning sources. Although environmental contaminants have been linked to health conditions in the past, direct work assessing air pollution exposure to prenatal bone development is inconclusive. Therefore, the purpose of this supplement is to 1) elucidate the impact of air pollutants on osteogenesis; 2) determine relevant miRNAs related to toxicant exposure and how it impacts bone development; 3) discern specific endocrine-disrupting chemicals found within air pollution; and 4) bring back findings to the communities that it may be impacting. This will be accomplished through direct exposure of pollution to osteogenically-differentiating human embryonic stem cells (hESCs), stained time-lapsed image quantification of mineralization phenotype, determining alterations of mRNA expression throughout differentiation, miRNA-sequencing analysis, and GC/MS data to quantify chemicals within samples. The work proposed within this supplement will be the first study of its kind to demonstrate perturbed osteogenesis in response to air pollution exposure. Additionally, this work will address the gap in knowledge of the dysregulation of miRNAs and resulting bone birth defects. In conjunction with an established human in vitro model and miRNA sequencing analysis, this supplement will continue to advance the evolving fields of molecular toxicology, reproductive toxicology, developmental toxicology, and bioinformatics, as was described in the parent grant. By completion of these studies, I expect to determine a causal relationship between prenatal air pollution exposure and skeletal birth defects. The implications of this work can reach beyond the science community, as these findings may aid in the development of prenatal check-up scans and help inform exposure policies in relation to congenital birth defects.

项目摘要与健康相关问题的影响被认为与具有密集空气污染的地区成比例。空气污染然而，成分高度基于污染区域，由一般污染物（例如气体）组成从排气，颗粒物和从燃烧来源释放的化合物。虽然环境过去污染物与健康状况有关，直接工作评估空气污染暴露于产前骨发育尚无定论。因此，该补充的目的是1）阐明空气污染物对成骨的影响； 2）确定与毒物暴露有关的相关miRNA及其如何影响骨骼发育； 3）辨别空气污染中发现的特定内分泌干扰化学物质；和4）将发现带回可能正在影响的社区。这将通过直接完成暴露于成骨分化的人类胚胎干细胞（hESC），染色的时间段矿化表型的图像定量，确定mRNA表达的改变分化，miRNA测序分析和GC/MS数据以量化样品中的化学物质。工作在此补充剂中提出的将是对此类研究的首次研究，以证明在对空气污染的反应。此外，这项工作将解决知识失调的差距 miRNA和由此产生的骨出生缺陷。结合建立的人类体外模型和miRNA 测序分析，这种补充剂将继续推进分子毒理学不断发展的领域，正如父母赠款所述，生殖毒理学，发育毒理学和生物信息学。经过这些研究的完成，我希望确定产前空气污染之间的因果关系和骨骼先天缺陷。这项工作的含义可以超越科学界，因为调查结果可能有助于制定产前检查扫描，并有助于告知有关暴露政策先天性先天缺陷。