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

• 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
• 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

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