Funk et al., 2021

The manuscript this repository has been published here: https://doi.org/10.1101/2021.12.19.473357 .

This directory contains scripts and files supporting the publication:

Funk et al., 2023, Aged intestinal stem cells propagate cell-intrinsic sources of inflammaging in mice, https://www.sciencedirect.com/science/article/pii/S1534580723006111 (2023) doi:10.1101/2021.12.19.473357

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.

Contact

Should you encounter any issues or have any questions please contact Maja C. Funk [email protected] or Florian Heigwer [email protected].

Raw sequencing read data are deposit at GEO under the Study ID: GSE190286

Directory information

The directory is structured by experiment:

All samples are epithelial cells from the mouse small intestine of young and aged mice:

in vivo single-cell RNA-Seq

in vivo bulk RNA-Seq

ex vivo bulk RNA-Seq

ex vivo ATAC-Seq

Each experiment folder contains a README file which provides the information on which notebook (folder "Scripts") was used to generate the plots and graphics to the respective experiment. These can be found in the folder "Graphics". The README file also explains to which exact figure the respective graphic/plot relates.