Format:
24
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Illustrationen
ISSN:
1878-1551
Content:
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.
Note:
Online verfügbar: 18. Dezember 2023, Artikelversion: 18. Dezember 2023
,
Gesehen am 08.04.2024
In:
Developmental cell, Cambridge, Mass. : Cell Press, 2001, 58(2023), 24 vom: Dez., Seite 2914-2929, 1878-1551
In:
volume:58
In:
year:2023
In:
number:24
In:
month:12
In:
pages:2914-2929
In:
extent:24
Language:
English
DOI:
10.1016/j.devcel.2023.11.013
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