| HRA003336
(Open Access)
|
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. |
