Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Fasting primes small intestinal regeneration after damage via a microbiome-metabolite-chromatin axis [RNA-seq]

ABSTRACT: Fasting protects the small intestine epithelial cells from high-dose radiation injury, yet the mechanisms linking fasting to epithelial regeneration remain incompletely understood. Akkermansia muciniphila (AKK) is both necessary and sufficient for fasting-induced radioprotection. Selective depletion of AKK abolishes fasting-mediated preservation of SI stem cells, while recolonization restores epithelial integrity and survival. AKK produces the short-chain fatty acid propionate, which, together with host-derived β-hydroxybutyrate (β-OHB), induces histone H3 acetylation (H3K27ac, H3K9ac) and β-hydroxybutyrylation (H3K9bhb) in crypt epithelial cells, remodeling enhancer–promoter landscapes. CUT&Tag and single-cell ATAC-seq analyses show that fasting, in an AKK-dependent manner, expands a Clu⁺Olfm4⁺ “revival” stem cell (persister cells) population enriched for HNF, FOXA, GATA and KLF transcription factor motifs, establishing a pro-regenerative chromatin state that persists through injury-repair phases. CTCF and BORIS activities persist, suggesting a role in maintaining epigenetic memory for intestinal regeneration after radiation. This microbiota–metabolite–chromatin axis primes persister cells for rapid regeneration after damage and offers a strategy to protect normal tissues during radiation therapy.

ORGANISM(S): Mus musculus

PROVIDER: GSE306576 | GEO | 2026/06/08

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Akkermansia muciniphila contributes to fasting-mediated radioprotection by inducing epigenetic and transcriptional changes in small intestinal epithelial cells

Project description:Fasting protects the small intestine epithelial cells from high-dose radiation injury, yet the mechanisms linking fasting to epithelial regeneration remain incompletely understood. Akkermansia muciniphila (AKK) is both necessary and sufficient for fasting-induced radioprotection. Selective depletion of AKK abolishes fasting-mediated preservation of SI stem cells, while recolonization restores epithelial integrity and survival. AKK produces the short-chain fatty acid propionate, which, together with host-derived β-hydroxybutyrate (β-OHB), induces histone H3 acetylation (H3K27ac, H3K9ac) and β-hydroxybutyrylation (H3K9bhb) in crypt epithelial cells, remodeling enhancer–promoter landscapes. CUT&Tag and single-cell ATAC-seq analyses show that fasting, in an AKK-dependent manner, expands a Clu⁺Olfm4⁺ “revival” stem cell (persister cells) population enriched for HNF, FOXA, GATA and KLF transcription factor motifs, establishing a pro-regenerative chromatin state that persists through injury-repair phases. CTCF and BORIS activities persist, suggesting a role in maintaining epigenetic memory for intestinal regeneration after radiation. This microbiota–metabolite–chromatin axis primes persister cells for rapid regeneration after damage and offers a strategy to protect normal tissues during radiation therapy.

2026-06-08 | GSE306673 | GEO

Fasting primes small intestinal regeneration after damage via a microbiome-metabolite-chromatin axis

2026-06-08 | GSE306671 | GEO

Fasting primes small intestinal regeneration after damage via a microbiome-metabolite-chromatin axis [Cut & Tag]

2026-06-08 | GSE306577 | GEO

Fasting enriched metabolic enhancers associate with histone lysine 9 ß-hydroxybutyrylation

Project description:β-hydroxybutyrate (β-OHB) is an essential metabolic energy source during fasting and functions as a chromatin regulator by lysine β-hydroxybutyrylation (Kbhb) modification of the core histones H3 and H4. We report that Kbhb on histone H3 (H3K9bhb) is enriched at proximal promoters of critical gene subsets associated with lipolytic and ketogenic metabolic pathways in small intestine (SI) crypts during fasting. Similar Kbhb enrichment is observed in Lgr5+ stem cell-enriched epithelial spheroids treated with β-OHB in vitro. Combinatorial chromatin state analysis reveals that H3K9bhb is associated with active chromatin states and that fasting enriches for an H3K9bhb-H3K27ac signature at active metabolic gene promoters and distal enhancer elements. Intestinal knockout of Hmgcs2 results in marked loss of H3K9bhb-associated loci, suggesting that local production of β-OHB is responsible for chromatin reprogramming within the SI crypt. We conclude that modulation of H3K9bhb in SI crypts is a key gene regulatory event in response to fasting.

2021-11-23 | GSE122896 | GEO

Akkermansia muciniphila reduces lipid absorption through activating AMPK in the jejunum

Project description:Akkermansia muciniphila (Akk) associated with multiple metabolic diseases and administration of Akk can improve the metabolic disorders. However, little is known about the effect of Akk on jejunal epithelial cells which absorb lipid and interact with oral administrated Akk. We oral administrated Akk to mice and measured the lipid absorption and gene expression in small intestinal epithelial cells. The long-term effect of Akk treatment reduced lipid deposits in the liver and adipocytes with improved the glucose metabolism. This is particularly caused by reduced lipid absorption in jejunal epithelia. Akk feeding reduced the expression of those genes that regulate synthesis and cell cycles, characters of the host cell responding to energy deficiency. In fact, we detected increased AMPK-alpha phosphorylation levels in Akk-treated jejunal epithelial cells both in vivo and in vitro. Furthermore, activating AMPK inhibits lipids absorption in jejunum. Thus, we conclude that oral administration of Akk activates the AMPK pathway and represses the lipid absorption in jejunal epithelial cells, which contributes to the metabolic benefits of oral Akk administration.

2025-01-25 | GSE254234 | GEO

Growth Factor Levels in the Blood of Patients Undergoing Radiation Therapy for Epithelial Cancer

Project description:RATIONALE: Measuring levels of transforming growth factor-beta (TGF-beta) in the blood of patients with epithelial cancers (head and neck, lung, breast, colorectal, and prostate) may help doctors predict how patients will respond to treatment with radiation therapy. PURPOSE: This research study is measuring levels of TGF-beta in patients with epithelial cancers who are undergoing radiation therapy.

| 2072028 | ecrin-mdr-crc

Adipocytes-derived β-hydroxybutyrate confers the resistance of myeloma cells to metabolic stress

Project description:Albeit being recognized as one of the major mesenchymal cells and a dangerous accomplice in myeloma, the roles of adipocytes in different stages of myeloma pathogenesis remain elusive. Here we showed that glucose metabolic stress impairs protein stability of interferon regulatory factor 4 (IRF4), an oncoprotein essential for myeloma cell survival, while adipocytes-derived β-hydroxybutyrate (β-OHB) preserves IRF4 stability and cell survival. Mechanistically, glucose deficiency activates the AMP-activated protein kinase (AMPK) to disrupt the interaction of IRF4 with heat shock protein 90 (HSP90), enabling the E3 ligase TRIM21-mediated IRF4 ubiquitination degradation. The presence of β-OHB drives 3-oxoacid CoA-transferase 1 (OXCT1)-mediated ketolysis and facilitates N-acetyltransferase 10 (NAT10)-mediated IRF4 acetylation at lysine 87, which restores IRF4’s interaction with HSP90 and precludes TRIM21-mediated IRF4 degradation. Notably, targeting OXCT1 or NAT10 to interfere with β-OHB utilization displays a synergistic anti-myeloma effect in combination with AMPK activator both in vitro and in vivo. Our study thus positions adipocytes-derived β-OHB as a pivotal contributor that enables myeloma cells to overcome glucose metabolic stress and suggests viable therapeutic targets to be exploited for multiple myeloma treatment.

2025-06-23 | GSE290392 | GEO

β-Hydroxybutyrate Boosts Plant Immunity through Enhanced histone Kbhb Levels and Gene Expression Regulation [ATAC-seq]

Project description:We demonstrated functional differences between H3K9bhb and the well-studied H3K9ac, particularly in regulating immune-response genes in rice. Moreover, we show that exogenous application of β-hydroxybutyrate enhances disease resistance in rice by inducing H3K9bhb deposition and stimulating the expression of defense-related genes. Furthermore, we identified SRT1, SRT2, and HDA705 as key players in the removal of histone Kbhb in rice plants.

2025-06-07 | GSE294829 | GEO

β-Hydroxybutyrate Boosts Plant Immunity through Enhanced histone Kbhb Levels and Gene Expression Regulation [ChIP-seq]

2025-06-07 | GSE294828 | GEO

β-Hydroxybutyrate Boosts Plant Immunity through Enhanced histone Kbhb Levels and Gene Expression Regulation [RNA-seq]

2025-06-07 | GSE294824 | GEO