Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Enterocyte dedifferentiation drives colonic regeneration following irradiation injury [scRNA-seq]

ABSTRACT: The intestinal epithelium consistently exposes to various injuries and exhibits remarkable regenerative capacity. Although small intestinal regeneration has been extensively investigated, the mechanisms governing colonic regeneration remain poorly understood. Here, we identify irradiation-induced regenerative cells (IRECs), a previously unrecognized colonic enterocyte population, emerges following irradiation injury. IRECs, marked by the gene YuanShangCao (Ysc), undergo dedifferentiation and transition into a stem-like state, contributing to epithelial regeneration. IREC ablation severely impairs colonic repair. Mechanistically, YSC promotes colonic regeneration by preventing the lysosomal degradation of YAP. Furthermore, we demonstrate a critical role of p53 in colonic regeneration by inducing Ysc expression. Together, our findings define IRECs as an irradiation injury-induced enterocyte population that dedifferentiate into stem cells in colon epithelial repair and establish the p53-YSC-YAP axis plays a key role in this process, deepening the understanding of colonic diseases.

ORGANISM(S): Mus musculus

PROVIDER: GSE274805 | GEO | 2025/08/16

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Enterocyte dedifferentiation drives colonic regeneration following irradiation injury [scRNA-seq]

Project description:Enterocyte dedifferentiation drives colonic regeneration following irradiation injury [scRNA-seq]

| PRJNA1148083 | ENA

Smooth muscle-specific MMP17 (MT4-MMP) defines the intestinal ECM niche

Project description:Smooth muscle is an essential component of the intestine, both to maintain its structure and produce peristaltic and segmentation movements. However, very little is known about other putative roles that smooth muscle may have. Here, we show that smooth muscle is the dominant supplier of BMP antagonists, which are niche factors that are essential for intestinal stem cell maintenance. Furthermore, muscle-derived factors can render epithelium reparative and fetal-like, which includes heightened YAP activity. Mechanistically, we find that the matrix metalloproteinase MMP17, which is exclusively expressed by smooth muscle, is required for intestinal epithelial repair after inflammation- or irradiation-induced injury. Furthermore, we provide evidence that MMP17 affects intestinal epithelial reprogramming indirectly by cleaving the matricellular protein PERIOSTIN, which itself is able to activate YAP. Together, we identify an important signaling axis that firmly establishes a role for smooth muscle as a modulator of intestinal epithelial regeneration and the intestinal stem cell niche.

2021-11-02 | PXD025770 | Pride

Smooth muscle-specific MMP17 (MT4-MMP) defines the intestinal ECM niche

2021-11-02 | PXD020561 | Pride

Arachidonic acid promotes intestinal regeneration by activating Wnt signaling

Project description:We identify arachidonic acid (AA), as a direct proliferation promoter of intestinal epithelial cells, facilitating small intestinal regeneration. In the transcriptomes, it shows that AA treatment upregulated proliferation-related genes including Wnt signaling target genes, while downregulated differentiation-related genes including enterocyte, goblet cell, Paneth cell, enteroendocrine cell, and tuft cell markers. Additionally, AA could also upregulate stem cell-associated genes which have been highly expressed three days after 12Gy IR injury (e.g. Clu, Lamc2, Anxa1, Areg, and Ly6d). The study shows that AA treatment can be considered a potential therapy for irradiation injury repair and tissue regeneration.

2020-07-27 | GSE146871 | GEO

Effect of NIBR-LTSi treatment on gene expression in mouse intestinal organoids

Project description:The YAP/Hippo pathway is a key regulator of organ growth and size regulation and is involved in safeguarding multiple tissue stem cell compartments. LATS kinases phosphorylate and thereby inactivate YAP, thus representing a potential direct drug target for promoting tissue regeneration. We report on the gene expression changes associated with YAP activation by the selective small molecule LATS kinase inhibitor NIBR-LTSi in mouse intestinal organoids. We show that, LATS-LTSi activates YAP signalling, promotes proliferation, induces a regenerative phenotype and blocks differentiation.

2024-03-07 | GSE240969 | GEO

ErbB2 drives Yap activation during cardiac regeneration

Project description:Cardiomyocyte (CM) loss after injury results in adverse remodelling and fibrosis, which inevitably lead to heart failure. Neuregulin-ErbB2 and Hippo-Yap signaling pathways are key mediators of CM proliferation and regeneration although the crosstalk between these pathways is unclear. Here, we demonstrate in mice that temporal over-expression (OE) of activated ErbB2 in CMs promotes cardiac regeneration in a heart failure model. Cellularly, OE CMs present an EMT-like regenerative response involving cytoskeletal reprograming, migration, ECM turnover, and displacement. Molecularly, we identified Yap as a critical mediator of ErbB2 signaling. In OE CMs, Yap interacts with nuclear envelope and cytoskeletal components, reflective of the altered mechanic state elicited by ErbB2. Hippo-independent activating phosphorylation on Yap at S352 and S274 were enriched in OE CMs, peaking during metaphase. Viral overexpression of Yap phospho-mutants dampened the proliferative competence of OE CMs. Taken together, we demonstrate a potent ErbB2-mediated Yap mechanosensory signaling involving EMT-like characteristics, resulting in heart regeneration.

2020-08-21 | PXD020731 | Pride

Melatonin Synergizes with Prostaglandin E2 to Enhance YAP-mediated Regenerative Epithelial Cell Emergence During Intestinal Repair

Project description:In this study, we explore the role of melatonin, abundantly secreted by enteroendocrine cells (EECs) yet overlooked beyond its circadian regulation, in promoting intestinal regeneration. Our findings demonstrate that melatonin can be integrated into the PGE2-EP4-YAP signaling axis to facilitate injury-responsive reprogramming and RSC induction in the intestinal epithelium both in vitro and in vivo. This work uncovers a novel function of melatonin, opening new therapeutic possibilities in regenerative medicine.

2025-03-31 | GSE293340 | GEO

Polyamines sustain epithelial regeneration of aged intestine

Project description:Aging reduces the regenerative capacity of the intestinal epithelium in different species including humans. The causes of delayed regeneration in the elderly remain unclear. Here, we used proteomic and metabolomic profiling of intestinal tissues together with functional assays to characterize the dynamics of regeneration following injury induced by 5-fluorouracil, a commonly used chemotherapeutic agent. Comparison of regeneration dynamics in mice of different ages revealed emergence of a proteostasis stress signature and increased levels of polyamines following injury exclusively in old epithelia. Mechanistically, we show that delayed regeneration is a cell-intrinsic feature of old epithelial cells that display reduced protein synthesis and accumulation of ubiquitylated proteins. We demonstrate that an intervention based on dietary restriction followed by re-feeding prior to injury elevates intracellular polyamine levels, alleviates proteostasis stress and restores the regenerative capacity of the old intestines. Our work provides novel targets and strategies to improve intestinal regeneration in the elderly.

2024-03-01 | MSV000094212 | MassIVE

Regenerative landscape of intestinal organoids (bulk RNA-Seq 1)

Project description:Development of intestinal organoids from single intestinal stem cells is driven by the regenerative capacity of the intestinal epithelium. To unravel molecular mechanisms orchestrating organoid formation and self-organization, we developed a high-content image-based screening assay for an annotated compound library. We generated multivariate feature profiles for hundreds of thousands of individual organoids to quantitatively describe the phenotypic landscape of organoid development. Generated phenotypic fingerprints were then used to infer regulatory genetic interactions from a single screen, establishing a novel paradigm in genetic interaction screening applied to an emergent system. This allowed the identification of novel modules of genes that regulate cell identity transitions and maintain the balance between regeneration and homeostasis. We then characterized a crucial role of retinoic acid nuclear receptors in controlling the exit from the regenerative state and in driving enterocyte differentiation. By combining quantitative imaging with RNA sequencing we confirmed the role of endogenous retinoic acid signaling and metabolism in initiating transcriptional programs guiding intestinal epithelium cell fate transitions and identified a small molecule inhibitor of retinoid x receptor, RXR, that improved intestinal regeneration in vivo. We use RNA sequencing to describe transcriptional changes induced in intestinal organoids cultured in presence of retinoic signaling modulators.

2020-05-22 | GSE134755 | GEO

ARID3A coordinates the proliferation-differentiation switch of transit-amplifying cells in the intestine

Project description:Intestinal stem cells (ISCs) at the crypt base divide and give rise to progenitor cells that have the capacity to proliferate and differentiate into various mature epithelial cell types in the transit-amplifying (TA) zone. Here, we identified the transcription factor ARID3A as a novel regulator of intestinal epithelial cell proliferation and differentiation at the TA compartment. We show that ARID3A forms an expression gradient from villus tip to the early progenitors at the crypts mediated by TGF-β and WNT signalling. Intestinal epithelial-specific deletion of Arid3a reduces proliferation of TA cells. Bulk and single cell transcriptomic analysis shows increased enterocyte differentiation and reduced secretory cells in the Arid3a cKO intestine. Interestingly, upper-villus gene signatures of both enterocytes and secretory cells are enriched in the mutant intestine. We find that the enhanced enterocyte differentiation in the Arid3a cKO intestine is caused by increased binding of HNF1 and HNF4. Finally, we show that loss of Arid3a impairs irradiation-induced regenerative process by altering the dynamics of proliferation and apoptosis. Our findings imply that ARID3A may play a gatekeeping role in the TA compartment to maintain the “just-right” proliferation-to-differentiation ratio for tissue homeostasis and plasticity

2024-07-31 | GSE243155 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data