Exploring chromatin state changes during liver aging and their impact on regeneration

探索肝脏衰老过程中染色质状态的变化及其对再生的影响

• 批准号: 10467890
• 负责人: Payel Sen
• 金额: $ 11.11万
• 依托单位: NATIONAL INSTITUTE ON AGING
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10467890
• 关键词: 3-Dimensional; Aging; Architecture; Cell Differentiation process; Characteristics; Chromatin; Data; Development; Epigenetic Process; Future; Genes; Genome; Impairment; Liver; Liver Regeneration; Mammals; Maps; Methods; Modeling; Molecular Conformation; Mus; Natural regeneration; Organ; Organoids; Pattern; Regenerative capacity; Signal Transduction; Structure; Testing; Work; age related; aged; cdc Genes; genome-wide analysis; histone modification; in vitro regeneration; morphogens; promoter; regeneration function; regeneration model; transcriptome; transcriptome sequencing

In the past year, we have analyzed our H3K27me3 data in aging and regenerating livers and correlated it to expression changes. Our data reveal two patterns of H3K27me3 alterations in aging: (1) formation of broad megabase-sized domains across the genome and (2) loss of signal at promoters of genes encoding developmental and cell differentiation factors. Micro-C results corroborate our findings with results indicating repressive compartment and TAD structures. We have also established two liver organoid models that we will use in the future to investigate age-related changes further.

在过去的一年中，我们分析了衰老和再生肝脏中的 H3K27me3 数据，并将其与表达变化相关联。我们的数据揭示了衰老过程中 H3K27me3 改变的两种模式：（1）在整个基因组中形成宽大的兆碱基大小的结构域；（2）编码发育和细胞分化因子的基因启动子信号丢失。 Micro-C 结果证实了我们的发现，结果显示了抑制室和 TAD 结构。我们还建立了两个肝脏类器官模型，我们将在未来使用它们进一步研究与年龄相关的变化。