| First Author | Funk MC | Year | 2023 |
| Journal | Dev Cell | Volume | 58 |
| Issue | 24 | Pages | 2914-2929.e7 |
| PubMed ID | 38113852 | Mgi Jnum | J:343769 |
| Mgi Id | MGI:7570045 | Doi | 10.1016/j.devcel.2023.11.013 |
| Citation | Funk MC, et al. (2023) Aged intestinal stem cells propagate cell-intrinsic sources of inflammaging in mice. Dev Cell 58(24):2914-2929.e7 |
| abstractText | Low-grade chronic inflammation is a hallmark of ageing, associated with impaired tissue function and disease development. However, how cell-intrinsic and -extrinsic factors collectively establish this phenotype, termed inflammaging, remains poorly understood. We addressed this question in the mouse intestinal epithelium, using mouse organoid cultures to dissect stem cell-intrinsic and -extrinsic sources of inflammaging. At the single-cell level, we found that inflammaging is established differently along the crypt-villus axis, with aged intestinal stem cells (ISCs) strongly upregulating major histocompatibility complex class II (MHC-II) genes. Importantly, the inflammaging phenotype was stably propagated by aged ISCs in organoid cultures and associated with increased chromatin accessibility at inflammation-associated loci in vivo and ex vivo, indicating cell-intrinsic inflammatory memory. Mechanistically, we show that the expression of inflammatory genes is dependent on STAT1 signaling. Together, our data identify that intestinal inflammaging in mice is promoted by a cell-intrinsic mechanism, stably propagated by ISCs, and associated with a disbalance in immune homeostasis. |
