Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Discrete WT1-positive hepatic fibrogenic cell lineages of distinct developmental mesothelial origin are paradoxically inhibited by WT1

ABSTRACT: Activated hepatic stellate cells orchestrate scar formation during fibrotic liver injury. Recent evidence has shown limited quiescent precursor derivation from the mesoderm during development. Here, we use lineage-tracing from development, through adult homeostasis, to adult fibrotic injury, to show that discreet subpopulations of activated hepatic stellate cells are defined by expression of WT1, a transcription factor controlling morphological transitions in organogenesis and adult homeostasis. Morphologically and transcriptionally distinct subpopulations are evident in fibrotic human disease and animal models. Populations defined by WT1 expression after injury derive from a discreet population of quiescent adult precursors originating from the embryonic mesothelium. WT1-deletion permits morphological transition to an enhanced fibrotic myofibroblast phenotype. Our findings demonstrate functional heterogeneity of adult scar-forming cells that can be whole-life traced back through specific quiescent precursors in adult homeostasis to differential origin in development, and defines WT1 as a paradoxical anti-fibrotic regulator during adult injury.

ORGANISM(S): Mus musculus

PROVIDER: GSE103103 | GEO | 2019/08/21

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Whole genome expression analysis of subpopulations of activated hepatic stellate cells defined by WT1 expression

Project description:Transciptional heterogeneity of scar-orchestrating cells in liver fibrosis, defined by WT1 expression, after chronic tetrachloride injury in vivo (WT1-high and WT1-low) or activation in vitro (WT1-negative).

2019-08-21 | GSE103055 | GEO

N-degradomic analysis of proteolytic processing in WT1 heterozygous mice

Project description:N-degradomic analysis of proteolytic processing in WT1 heterozygous mice, suffering from genetically induced chronic kidney injury, compared to wild type

2021-02-15 | PXD023292 | Pride

WT1+ parietal epithelial progenitor cells are essential for renal proximal tubule repair and regeneration

Project description:Purpose: We have found that WT1+ parietal epithelial progenitor cells contribute to renal proximal tubule repair and regeneration by cell lineage tracing and direct differentiation analysis, but the transcription profile of these WT1+ PECs is largely unkown. Here, we aimed to unveil the transcriptional features of WT1+ PECs through single-cell RNA sequencing (scRNA-seq). Methods: Single cell suspension was prepared from kidney cortex of WT1CreERT2; Rosa26-tdTfl/+ mice that underwent sham or ischemic reperfusion injury (IRI) 24h .TdT+ cells were enriched by fluorescence activated cell sorter (FACS) and further analyzed with BD Rhapsody platform. Results: After quality control and cell filtering, 26,759 cells were informative (Dataset S1) and divided into 10 clusters using Harmony algorithm to reduce batch effects. GO analysis and QuSAGE heatmap suggested that WT1+ PECs might promote kidney regeneration after AKI through TGF-β and Notch signaling pathway. Marker gene expression analysis showed that WT1+ PECs shared the characteristics of STCs. Pseudotemporal analysis indicated that that WT1+ PECs developed to PTECs through STCs intermediate stage. Conclusions: scRNA-seq indicated that the rare, quiescent PECs supplied PTECs through STCs intermediate stage after severe ischemic injury, and this process most likely was regulated through TGF-β and Notch signaling pathway.

2023-03-22 | GSE184601 | GEO

WT1 mutations in T-ALL

Project description:The molecular mechanisms involved in disease progression and relapse in T-cell acute lymphoblastic leukemia (T-ALL) are poorly understood. We used single nucleotide polymorphism (SNP) array analysis to analyze paired diagnostic and relapsed T-ALL samples to identify recurrent genetic alterations in T-ALL. This analysis showed a notorious absence of acquired chromosomal changes at relapse. In addition, we identified deletions and associated mutations in the WT1 tumor suppressor gene in 2/9 samples. Subsequent analysis showed WT1 mutations in 28/211 (13.2%) of pediatric and 10/85 (11.7%) of adult T-ALL cases. WT1 mutations present in T-ALL are predominantly heterozygous frameshift mutations resulting in truncation of the C-terminal zinc finger domains of this transcription factor. WT1 mutations are most prominently found in T-ALL cases with aberrant rearrangements of the oncogenic TLX1, TLX3 and HOXA transcription factor oncogenes. Survival analysis demonstrated that WT1 mutations do not confer adverse prognosis in pediatric and adult T-ALL. Overall these results show that overt chromosomal instability does not seem to be a major mutagenic mechanism contributing to disease progression in T-ALL and the presence of WT1 mutations as a recurrent genetic alteration in T-ALL.

2009-08-10 | GSE15931 | GEO

Skin regeneration is enabled in the absence of fibroblast inflammatory priming

Project description:Mammalian skin wounds heal by forming fibrotic scars. We report that reindeer antler velvet exhibits regenerative wound healing, whereas identical injury to back skin forms scar. This regenerative capacity was retained following ectopic transplantation of velvet to scar-forming sites. Single-cell mRNA/ATAC-Sequencing revealed that while uninjured velvet fibroblasts resembled human fetal fibroblasts, back skin fibroblasts were enriched in pro-inflammatory features resembling adult human fibroblasts. Injury elicited site-specific immune polarization; back skin fibroblasts amplified the immune response, whereas velvet fibroblasts adopted an immunosuppressive state leading to restrained myeloid maturation and hastened immune resolution ultimately enabling myofibroblast reversion to a regeneration-competent state. Finally, regeneration was blunted following application of back skin associated immunostimulatory signals or inhibition of pro-regenerative factors secreted exclusive to velvet fibroblasts. This study highlights a unique model to interrogate mechanisms underlying divergent healing outcomes and nominates both decoupling of stromal-immune crosstalk and reinforcement of pro-regenerative fibroblast programs to mitigate scar.

2023-02-23 | PXD035749 | Pride

Expression data from HSCs

Project description:Hepatic stellate cells (HSCs) experience phenotypic transformation, from the quiescent phenotype to the activated one, after different etiologies of liver injury. Liver fibrosis is then occurred upon the activation of HSCs. miR-16 deficiency is identified to be an important characteristic of HSCs activation. We used Affymetrix rat 230 2.0 arrays (Affymetrix, Santa Clara, U.S.A.) to uncover the global alternations of transcriptome under miR-16 restoration. We isolated quiescent hepatic stellate cells (HSCs) from adult male SD rats (normal control group) by in situ perfusion and density-gradient centrifugation. Activated HSCs were separated from rats of fibrosis model group, which were treated by 40% carbon tetrachloride (CCl4) for 8 weeks, by means of liver section, digestion and sequential centrifugation. Quiescent and activated HSCs were then divided into 4 groups at random, namely quiescent HSCs, activated HSCs, pLV-miR-16-treated HSCs and pLV-GFP-treated HSCs. The pLV-miR-16-treated group, pLV-GFP-treated group were infected with pLV-miR-16 and pLV-GFP, respectively.

2012-08-28 | E-GEOD-40381 | biostudies-arrayexpress

FOXC2 and WT1 regulate transcriptional reprogramming during the podocyte response to injury

Project description:In the context of human disease, the mechanisms whereby transcription factors reprogram gene expression in reparative responses to injury are not well understood. We have studied the mechanisms of transcriptional reprogramming in disease using murine kidney podocytes as a model for tissue injury. Podocytes are a crucial component of glomeruli, the filtration units of each nephron. Podocyte injury is the initial event in many processes that lead to End Stage Kidney Disease. FOXC2 is a transcription factor known to regulate gene expression in podocytes. FOXC2 and WT1 are both required for podocyte differentiation. Using murine models and human kidney organoids, we investigated FOXC2-mediated transcriptional reprogramming during the course of podocyte injury. Correlating FOXC2 and WT1 ChIP-seq analyses demonstrated that they co-bind many genes expressed in podocytes. Reprogramming the transcriptome involved highly dynamic changes in the binding of FOXC2 and WT1 to target genes during a reparative injury response.

2023-11-01 | GSE213174 | GEO

Post-transcriptional Fibroblast Fate Switching By MBNL1 Regulates Fibrotic and Myocardial Remodeling During Cardiac Wound Healing

Project description:Dynamic fibroblast state transitions underlie the heart’s fibrotic response, raising the possibility that tactical control of these transitions could alter maladaptive fibrotic outcomes. Transcriptome maturation by Muscleblind-like 1 (MBNL1) has emerged as a driver of differentiated cell states. Indeed, MBNL1 expression is elevated in conjunction with profibrotic transcripts in lineage traced myofibroblasts and modeling this gain in function by fibroblast-specific overexpression of an MBNL1 transgene induced a myofibroblast transcriptional identity in healthy hearts and promoted maladaptive myocyte remodeling and scar maturation following injury. Both fibroblast-specific and myofibroblast-specific loss of MBNL1 limited scar production and maturation, which was ascribed to negligible myofibroblast activity. MBNL1 deletion drove expansion of all quiescent cardiac fibroblast states and promoted mesenchymal stem cell characteristics while forced MBNL1 expression restricted state diversity by transitioning most fibroblasts to the most mature myofibroblast identity. These data suggest MBNL1 is a post-transcriptional switch controlling quiescent to myofibroblast transitions during cardiac wound healing.

2022-01-20 | GSE193308 | GEO

Gene expression of pdgfrb+ cells in the intact and injured spinal cord.

Project description:Spinal cord injury (SCI) leads to fibrotic scar formation at the lesion site, which finally affects axon regeneration and motor functional recovery. Myofibroblasts have been regarded as the main cell types that filled in the fibrotic scar, however, the cell source of myofibroblasts in transection and crush SCI model remain to be elusive. Here we used lineage tracing or single cell transcription sequencing to investigate the cell origin of fibrotic scar. We found fibrotic scars were filled from PDGFRβ+ daughter cells in spinal cord in crush SCI or transection SCI. The parenchyma perivascular-derived and meninges-derived PDGFRβ+ fibroblasts, but not PDGFRβ+ pericytes, proliferated and contributed to fibrotic cells in the lesion core. The percentage of meninges-derived fibroblasts specifically was higher than parenchyma perivascular-derived fibroblasts in transection model, which might contribute to the more fibrotic scar in transection model than crush model. These findings may provide theoretical support for the treatment of spinal cord injury.

2024-06-07 | GSE218584 | GEO

Tricyclic Antidepressants Induce Inactivation of Hepatic Stellate Cell (HSC) Myofibroblasts

Project description:Hepatic stellate cells (HSCs) are the primary cell type responsible for liver fibrosis, the final common pathway leading to cirrhosis and liver failure for nearly every cause of chronic liver disease. Activation of HSCs in response to injury represents the key step in hepatic fibrogenesis, and is characterized by a phenotypic change from a non-fibrogenic, quiescent HSC to a fibrogenic HSC myofibroblast that secretes extracellular matrix proteins responsible for the fibrotic scar. We developed a small molecule screen to identify compounds that revert fibrotic human HSC myofibroblasts to an inactive phenotype through the quantification of lipid droplets with fluorescent microscopy. Conditions were optimized in a 384-well format using culture in Matrigel as a positive control. We screened 1600 compounds and identified 30 small molecules that induce reversion to an inactive phenotype. Among the hits, we identified five tricyclic antidepressants (TCAs) and showed that this class of drugs also repressed ACTA2 and COL1A1 while promoting PPAR-gamma expression. RNA sequencing analysis implicated extracellular matrix proteins and the sphingolipid pathway as a target of the TCAs.

2017-03-02 | GSE78853 | 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