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| Item Type: | Article |
|---|---|
| Title: | Aged intestinal stem cells propagate cell-intrinsic sources of inflammaging in mice |
| Creators Name: | Funk, M.C., Gleixner, J.G., Heigwer, F., Vonficht, D., Valentini, E., Aydin, Z., Tonin, E., Del Prete, S., Mahara, S., Throm, Y., Hetzer, J., Heide, D., Stegle, O., Odom, D.T., Feldmann, A., Haas, S., Heikenwalder, M. and Boutros, M. |
| Abstract: | 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. |
| Keywords: | Ageing, Inflammaging, ISC, Intestine, Single-Cell Analysis, Inflammation, Intestinal Stem Cells, Intestinal Epithelium, Interferon, Epigenetics, Animals, Mice |
| Source: | Developmental Cell |
| ISSN: | 1534-5807 |
| Publisher: | Cell Press |
| Volume: | 58 |
| Number: | 24 |
| Page Range: | 2914-2929 |
| Date: | 18 December 2023 |
| Official Publication: | https://doi.org/10.1016/j.devcel.2023.11.013 |
| PubMed: | View item in PubMed |
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