Mechanisms and determinants of dynamic gene regulation during development and cellular differentiation

发育和细胞分化过程中动态基因调控的机制和决定因素

• 批准号: 10491804
• 负责人: Sebastian Pott
• 金额: $ 41万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-21 至 2026-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10491804
• 关键词: Biological Models; Biomedical Research; Cells; Code; Development; Disease; Epigenetic Process; Gene Expression Regulation; Genetic; Genetic Transcription; Genome; Genomics; Heterogeneity; Homeostasis; Human; Human Genome; Individual; Malignant Neoplasms; Metabolic Diseases; Organism; Organoids; Pathology; Process; Regulator Genes; Sampling; Specific qualifier value; Stimulus; base; cell type; chronic inflammatory disease; genetic manipulation; human disease; human tissue; in vitro Model; induced pluripotent stem cell; multiple omics; pathogenic microbe; response; technology development; tool

PROJECT SUMMARY The human genome encodes information that specifies the development of an entire organism comprising at least 10 trillion cells and more than 200 different cell types. The genome also contains the information to direct appropriate responses to a host of environmental stimuli to maintain homeostasis and respond to challenges, e.g. from microbial pathogens. Changes to this code or dysregulation of its interpretation underlie almost all human diseases, including chronic inflammatory diseases, metabolic disorders, and cancer. Obtaining mechanistic and quantitative understanding of gene regulation in individual cells is a crucial prerequisite for a better understanding, and ultimately treatment, of diseases. Studying gene regulatory processes in human tissues has been challenging because of their cellular heterogeneity and because most human samples are not accessible to longitudinal observations and direct perturbations. However, the advent of single cell genomic technologies, the development of human iPSC and organoid-based in vitro model systems, and the availability of powerful tools for genetic perturbations have the potential to overcome these challenges and to revolutionize biomedical research. In this proposal we combine the development of single- cell multiomic tools that accurately profile multiple regulatory features within single cells or molecules with mechanistic and disease-focused studies to understand how genetic and environmental perturbations of gene regulatory processes disrupt cellular differentiation and underlie pathologies.

项目总结