Diet-induced chromatin states influence intestinal stem cell memory
Saiz, D. R.; Barrera Millan, Y.; Hartley McDermott, T.; Cerna, G.; Sankar, S.; Farnsworth, F.; Uher, E.; Lahiri, G.; Lintecum, K.; Mullen, K.; Bartelle, B. B.; Mana, M. D.
Show abstract
Intestinal stem cells (ISCs) integrate dietary cues through a metabolic-transcriptional axis, but whether these mechanisms create a lasting epigenetic memory remains unclear. Here, we investigate diet-induced chromatin adaptations in ISCs using a high-fat Western diet (HFD) mouse model. HFD broadly remodels chromatin accessibility, altering pre-existing open regulatory regions. Many differentially accessible regions (DARs) persist during the differentiation of ISCs into transient amplifying cells (TACs). Notably, HFD-induced DARs are retained following diet normalization despite phenotypic reversibility, and HFD re-exposure enhances ISC self-renewal and adenoma growth compared with naive HFD exposure. The HFD-induced chromatin changes require Ppar-d/a nuclear receptors but are independent of their transcriptional targets. Although a subset of HFD-induced DARs is maintained following Apc loss, extensive chromatin remodeling driven by tumor suppressor inactivation largely overrides diet-dependent differences in Lgr5 ISCs. Together, these findings demonstrate that ISCs retain a chromatin-based memory of dietary fat exposure.
Matching journals
The top 4 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Dietary fibers benefits on glucose homeostasis require type 2 conventional dendritic cells in mice fed a high-fat diet 96%
- A MTA2-SATB2 chromatin complex restrains colonic plasticity toward small intestine by retaining HNF4A at colonic chromatin 96%
- Integrated genomic analysis of AgRP neurons reveals that IRF3 regulates leptin's hunger-suppressing effects 95%
Similar papers in this journal
Similar papers in this journal
- LSD1 represses a neonatal/reparative gene program in adult intestinal epithelium 96%
- Transcriptional and epigenomic profiling identifies YAP signaling as a key regulator of intestinal epithelium maturation 95%
- Aberrant cell state plasticity mediated by developmental reprogramming precedescolorectal cancer initiation 95%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.