| 项目编号 | PRJCA012536 | ||||||||
|---|---|---|---|---|---|---|---|---|---|
| 项目标题 | Sirtuins modulate sub-TAD organization and repress placenta-specific genes that drive cellular aging | ||||||||
| 涉及领域 | Model organism | ||||||||
| 数据类型 |
Whole genome sequencing
Epigenomics Transcriptome or Gene expression |
||||||||
| 物种名称 | Homo sapiens | ||||||||
| 描述信息 | Stem cell exhaustion is the hallmark of aging, but the molecular mechanisms underlying Sirtuins in mesenchymal stem cells (hMPCs) have remained inconclusive. By constructing human embryonic stem cell (hESCs) with Sirtuins deficiency and differentiated into hMPCs, we observed that Sirtuins-deficient hMPCs exerted different degrees of accelerated senescence phenotypes, with their nuclear structure abnormalities and chromatin disorder. Here, we integrated epigenomic, three-dimensional genome, and transcriptomic analyses of Sirtuins-deficient hMPCs to identify molecular pathways involved in human stem cell aging. We found that the chromatin states of hMPCs after Sirtuins deficiency tend to shift to an activated state with a broad spectrum of increased acetylation levels, and these increases are mostly distributed in the distal end. From the chromatin high-level structure, SIRT1-7 deficiency triggers common epigenetic alterations, as evidenced by increased TAD internal interactions, enhanced loop interactions, and enrichment of activating chromatin signals. Our research uses 3D chromatin organization landscape of human stem cells to establish the connections between Sirtuins and their putative target effector genes, founding the placental specific gene PAPPA was a potential driving force for regulating the aging process. | ||||||||
| 样品范围 | Multiisolate | ||||||||
| 发布日期 | 2023-05-22 | ||||||||
| 项目资金来源 |
|
||||||||
| 提交者 | Jing Qu (qujing@ioz.ac.cn) | ||||||||
| 提交单位 | Institute of Zoology, Chinese Academy of Sciences | ||||||||
| 提交日期 | 2022-10-16 |
| 资源名称 | 描述 |
|---|---|
| BioSample (394) show | - |