Tomita-Naito Saki, Sulekh Shivakshi, Yoo Sa Kan
Laboratory for Homeodynamics, RIKEN BDR, Kobe, Japan.
Graduate School of Frontier Biosciences, Osaka University, Osaka, Japan.
iScience. 2024 Sep 9;27(9):110793. doi: 10.1016/j.isci.2024.110793. eCollection 2024 Sep 20.
During aging, tissue stem cells can demonstrate two opposing phenotypes of tissue homeostasis disruption: proliferation and exhaustion. Stem cells can exhaust as a result of excessive cell proliferation or independently of cell proliferation. There are many silent changes in chromatin structures and gene expression that are not necessarily reflected in manifested phenotypes during aging. Here through analyses of chromatin accessibility and gene expression in intestinal progenitor cells during aging, we discovered changes of chromatin accessibility and gene expression that have a propensity to exhaust intestinal stem cells (ISCs). During aging, Trithorax-like (Trl) target genes, and , close their chromatin structures and decrease their expression in intestinal progenitor cells. Inhibition of , , or exhausts ISCs. This study provides new insight into changes of chromatin accessibility and gene expression that have a potential to exhaust ISCs during aging.
在衰老过程中，组织干细胞会表现出两种破坏组织稳态的相反表型：增殖和耗竭。干细胞可能由于过度的细胞增殖或独立于细胞增殖而耗竭。在衰老过程中，染色质结构和基因表达存在许多沉默变化，这些变化不一定会在明显的表型中体现出来。在这里，通过对衰老过程中肠道祖细胞的染色质可及性和基因表达进行分析，我们发现了染色质可及性和基因表达的变化，这些变化倾向于使肠道干细胞（ISC）耗竭。在衰老过程中，类三胸蛋白（Trl）靶基因和在肠道祖细胞中关闭其染色质结构并降低其表达。抑制或会使ISC耗竭。这项研究为衰老过程中可能导致ISC耗竭的染色质可及性和基因表达变化提供了新的见解。
