Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Potential landscape decomposes the cell identity conversion in liver regeneration and tumorigenesis [ChIP-seq]

ABSTRACT: Tumorigenesis, accompanied by tissue regenerative responses, always occurs during mammalian organ injury. In liver, injury context promotes dedifferentiated liver progenitor-like cells (LPLCs) from hepatocytes for regeneration, and also increases the occurrence of hepatocellular carcinoma (HCC). However, little is known about the contribution of injury specific LPLCs to tumorigenesis. Here, by using lineage tracing model, we have demonstrated that LPLCs are highly susceptible to oncogene-induced tumorigenesis. By using quantitative landscape of differentiation dynamics (LDD) model, we have constructed potential landscape of liver regeneration and tumorigenesis via scRNA-seq data, in order to predict distinct regulations of cell fate decisions. Applying this landscape with in vivo validation by transgenic mouse model, we have found blocking Wnt activation not only inhibits tumorigenesis, but also decreases LPLCs. Surprisingly, by using least action pathway analysis, we have decomposed regeneration and tumorigenesis routes, and found EP300 is specifically involved in tumorigenesis, which is further supported by in vivo EP300-knockout model and EP300 inhibitor assays. These findings might be applied as a framework to find tumor-specific regulators and develop strategies specifically inhibiting tumor initiation while leaving tissue regeneration unaffected.

ORGANISM(S): Mus musculus

PROVIDER: GSE244909 | GEO | 2024/09/29

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Potential landscape decomposes the cell identity conversion in liver regeneration and tumorigenesis [scRNA-seq]

Project description:Tumorigenesis, accompanied by tissue regenerative responses, always occurs during mammalian organ injury. In liver, injury context promotes dedifferentiated liver progenitor-like cells (LPLCs) from hepatocytes for regeneration, and also increases the occurrence of hepatocellular carcinoma (HCC). However, little is known about the contribution of injury specific LPLCs to tumorigenesis. Here, by using lineage tracing model, we have demonstrated that LPLCs are highly susceptible to oncogene-induced tumorigenesis. By using quantitative landscape of differentiation dynamics (LDD) model, we have constructed potential landscape of liver regeneration and tumorigenesis via scRNA-seq data, in order to predict distinct regulations of cell fate decisions. Applying this landscape with in vivo validation by transgenic mouse model, we have found blocking Wnt activation not only inhibits tumorigenesis, but also decreases LPLCs. Surprisingly, by using least action pathway analysis, we have decomposed regeneration and tumorigenesis routes, and found EP300 is specifically involved in tumorigenesis, which is further supported by in vivo EP300-knockout model and EP300 inhibitor assays. These findings might be applied as a framework to find tumor-specific regulators and develop strategies specifically inhibiting tumor initiation while leaving tissue regeneration unaffected.

2024-09-29 | GSE244911 | GEO

Potential landscape decomposes the cell identity conversion in liver regeneration and tumorigenesis [RNA-seq]

2024-09-29 | GSE244910 | GEO

A homeostatic Arid1a-dependent permissive chromatin state licenses hepatocyte responsiveness to liver injury-associated YAP signaling (RNA-seq)

Project description:Following injury, differentiated epithelial cells can serve as a stem cell-independent source for tissue regeneration by undergoing reprogramming into other cell types. The intrinsic molecular basis underlying plasticity of differentiated cells remains largely unaddressed. Here we show that Arid1a, a key component of the SWI/SNF chromatin remodeling complex, controls liver regeneration and gene expression associated with emergence of injury-induced progenitor-like cells (LPLCs). Hepatocyte-specific Arid1a ablation reduces LPLC gene expression in several models of periportal liver injury and impairs liver regeneration, leading to organ dysfunction. Arid1a establishes a permissive chromatin state at LPLC-enriched genes during homeostasis, suggesting it endows hepatocytes with competence to respond to injury-induced signals. Consistently, Arid1a facilitates binding of YAP, a critical regeneration signaling pathway, to LPLC-enriched genes, and Arid1a deletion prevents their YAP-associated induction following injury. Together, these findings provide a framework for studying the contributions of injury-induced LPLCs to periportal liver regeneration.

2019-07-07 | GSE111501 | GEO

A homeostatic Arid1a-dependent permissive chromatin state licenses hepatocyte responsiveness to liver injury-associated YAP signaling (ChIP-seq)

2019-07-07 | GSE111500 | GEO

A homeostatic Arid1a-dependent permissive chromatin state licenses hepatocyte responsiveness to liver injury-associated YAP signaling (ATAC-seq)

2019-07-07 | GSE111499 | GEO

Macrophages trigger injury-induced hepatocyte reprogramming via IL-6/gp130/STAT3 axis [RNA-Seq]

Project description:The liver is a pivotal organ possessing remarkable regenerative capacity. By employing murine liver injury models and lineage tracing strategy, recent studies have demonstrated that differentiated hepatocytes undergo reprogramming to SOX9+HNF4α+ liver progenitor-like cells (LPLCs), and serve as a totally new cell source for mammalian liver regeneration. However, it is largely unknown how hepatocyte reprogramming is regulated. In this study, we focus on analyzing the microenvironment cues in triggering hepatocyte reprogramming in liver injuries. By performing single-cell RNA sequencing (scRNA-seq) of hepatocyte reprogramming in liver injury, we find immune response is significantly activated. Notably, by lineage depletion, macrophages, especially kupffer cells, but not T cells, B cells, natural killer cells or neutrophils, are found essential for hepatocyte reprogramming and liver regeneration. IL-6, derived specifically from activated kupffer cells, triggers hepatocyte reprogramming via gp130/STAT3 signaling. Furthermore, STAT3 triggers gene expression by binding to Arid1a-dependent pre-opened regeneration-responsive enhancers (RREs) of reprogramming genes. Collectively, this study provides key insights into kupffer cells/IL-6/STAT3-mediated hepatocyte reprogramming and liver regeneration, which may serve as the base for new therapeutic strategies in facilitating endogenous repair mechanisms.

2022-08-24 | GSE193849 | GEO

Macrophages trigger injury-induced hepatocyte reprogramming via IL-6/gp130/STAT3 axis [ChIP-Seq]

2022-08-24 | GSE193848 | GEO

Single-cell RNA sequencing decipher hepatic injury and APOA4 as a biomarker in males with intrauterine growth restriction

Project description:<p>Intrauterine growth restriction (IUGR) is associated with increased relative liver weight at birth, hepatic function decline and a higher risk for chronic liver and cardiovascular diseases in adults. Precise mechanisms of early developmental plasticity to intervene in poor fetal programming and adult disease remain largely elusive and warrant extensive research. Selecting natural piglets’ model of IUGR, using the liver as a readout and combining previous transcriptome findings, a map of cellular landscape was created to reveal a sex-dependent manner in IUGR-induced hepatic injury and its long-term functional repercussions. At the one-week postnatal node, we reveal that in contrast to a converting trend about an immune-adapted phenotype in female IUGRs, the more severe hepatic injury in male IUGRs is attributed to persistent inflammation caused by abnormal lipid metabolism, which disrupts the interactions of non-immune cells, resulting in impaired liver regeneration lasting into adulthood. In addition, we consider APOA4 as a new biomarker for the detection of IUGRs and discover its underlying role in hypoxic conditions. Our study opens the possibility to early therapy and screening of gender-specific hepatic injury brought on by IUGR.</p>

2023-09-25 | MTBLS6881 | MetaboLights

Potential landscape decomposes the cell identity conversion in liver regeneration and tumorigenesis

Project description:Potential landscape decomposes the cell identity conversion in liver regeneration and tumorigenesis

| PRJNA1026103 | ENA

Transcriptional analysis of in vivo responses to acetaminophen induced hepatic injury in the murine liver

Project description:Liver injury results in rapid regeneration through hepatocyte proliferation and hypertrophy. However, after acute severe injury, such as acetaminophen poisoning, effective regeneration may fail. We investigated how senescence underlies this regenerative failure. In human acute liver disease, and murine models, p21-dependent hepatocellular senescence was proportionate to disease severity and was associated with impaired regeneration. In an acetaminophen injury model a transcriptional signature associated with the induction of paracrine senescence is observed within twenty four hours, and is followed by one of impaired proliferation. In genetic models of hepatocyte injury and senescence we observed transmission of senescence to local uninjured hepatocytes. Spread of senescence depended upon macrophage derived TGFβ1 ligand. In acetaminophen poisoning inhibition of TGFβ receptor 1 (TGFβR1) improved survival. TGFβR1 inhibition reduced senescence and enhanced liver regeneration even when delivered after the current therapeutic window. This mechanism, in which injury induced senescence impairs regeneration, is an attractive therapeutic target for acute liver failure.

2019-03-20 | GSE111828 | 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