Hyper-activated Wnt-β-catenin signaling in the absence of sFRP1 and sFRP5 represses Mash2 expression derailing normal spongiotrophoblast differentiation
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA610571 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR11244977_1.fastq.gz | Fastqsanger.gz | |||
| SRR11244977_2.fastq.gz | Fastqsanger.gz | |||
| SRR11244978_1.fastq.gz | Fastqsanger.gz | |||
| SRR11244978_2.fastq.gz | Fastqsanger.gz | |||
| SRR11244979_1.fastq.gz | Fastqsanger.gz |
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Project description:This SuperSeries is composed of the SubSeries listed below.
2020-03-06 | GSE146434 | GEO
Project description:Idiopathic pulmonary fibrosis (IPF) is a lethal chronic lung disease characterized by aberrant intercellular communication, extracellular matrix deposition and destruction of functional lung tissue. While extracellular vesicles (EVs) accumulate in the IPF lung, their cargo and biological effects remain unclear. We interrogated the proteome of EV and non-EV fractions during pulmonary fibrosis and characterize their contribution to fibrosis. EVs accumulated 14 days post-bleomycin challenge, correlating with decreased lung function and initiated fibrogenesis in healthy precision-cut lung slices. Label-free proteomics of broncho-alveolar lavage fluid (BALF)-EVs collected from mice challenged with bleomycin or control identified 107 proteins enriched in fibrotic vesicles. Multiomic analysis revealed fibroblasts as a major cellular source of BALF-EV cargo, which was enriched in Secreted Frizzled Related Protein 1 (SFRP1). Sfrp1 deficiency inhibited the activity of fibroblast-derived EVs to potentiate lung fibrosis in vivo. SFRP1 led to increased transitional cell markers, such as Krt8, and WNT/β-catenin signaling in primary alveolar type 2 cells. SFRP1 is expressed within the IPF lung and localized at the surface of EVs from patient-derived fibroblasts and BALF. Our work reveals altered EV protein cargo in fibrotic EVs promoting fibrogenesis and identifies fibroblast derived vesicular SFRP1 as fibrotic mediator and potential therapeutic target for IPF.
2024-11-05 | GSE272679 | GEO
Project description:Sfrp1 is a Wnt inhibitor that is down regulated in various human cancers such as acute myeloid leukaemia, hepatocellular carcinoma, pancreatic, ovarian and breast cancer etc. Our study has shown that the loss of Sfrp1 in mouse skin leads to early tumor initiation with induced skin chemical carcinogenesis. Further, CSCs isolated from the Sfrp1-/- tumors showed increased in vivo tumorigenic potential with enhanced tumor propagating cell (TPC) frequency when injected into NOD/SCID mice. Hence, in order to understand the molecular mechanism involved in CSC regulation in the absence of sfrp1, we have performed microarray analysis on CSCs isolated from mice skin SCC. The data showed upregulation of genes involved in the regulation of tumor aggressiveness, metastasis and stemness in Sfrp1-/- CSCs as compared to WT CSCs. Our study has provided significant contribution to the existing knowledge of Sfrp1 by showing the uncharted role of Sfrp1 in tumor initiation and CSC regulation.
2020-01-30 | GSE141176 | GEO
Project description:Fibroblast to myofibroblast conversion is a major driver of tissue remodeling in organ fibrosis. Several distinct lineages of fibroblasts support homeostatic tissue niche functions, yet, specific activation states and phenotypic trajectories of fibroblasts during injury repair have remained unclear. Here, we combined spatial transcriptomics, longitudinal single-cell RNA-seq and genetic lineage tracing to study fibroblast fates during mouse lung regeneration. We discovered a transitional fibroblast state characterized by high Sfrp1 expression, derived from both Tcf21-Cre lineage positive and negative cells. Sfrp1+ cells appeared early after injury in peribronchiolar, adventitial and alveolar locations and preceded the emergence of myofibroblasts. We identified lineage specific paracrine signals and inferred converging transcriptional trajectories towards Sfrp1+ transitional fibroblasts and Cthrc1+ myofibroblasts. Tgfβ1 downregulated Sfrp1 in non-invasive transitional cells and induced their switch to an invasive Cthrc1+ myofibroblast identity. Finally, using loss of function experiments we show that autocrine Sfrp1 directly inhibits fibroblast invasion by regulating the RhoA pathway. In summary, our study reveals the convergence of spatially and transcriptionally distinct fibroblast lineages into transcriptionally uniform myofibroblasts and identifies Sfrp1 as an autocrine inhibitor of fibroblast invasion during early stages of fibrogenesis.
2023-11-14 | GSE207561 | GEO
Project description:Fibroblast to myofibroblast conversion is a major driver of tissue remodeling in organ fibrosis. Here, we combined spatial transcriptomics, longitudinal single-cell RNA-seq and genetic lineage tracing to study fibroblast fates during mouse lung regeneration. We discovered a transitional fibroblast state characterized by high Sfrp1 expression, derived from both Tcf21-Cre lineage positive and negative cells. Sfrp1+ cells appeared early after injury in peribronchiolar, adventitial and alveolar locations and preceded the emergence of myofibroblasts. We identified lineage specific paracrine signals and inferred converging transcriptional trajectories towards Sfrp1+ transitional fibroblasts and Cthrc1+ myofibroblasts. Tgfβ1 downregulated Sfrp1 in non-invasive transitional cells and induced their switch to an invasive Cthrc1+ myofibroblast identity. Our study reveals the convergence of spatially and transcriptionally distinct fibroblast lineages into transcriptionally uniform myofibroblasts and identifies Sfrp1 as an autocrine inhibitor of fibroblast invasion during early stages of fibrogenesis.
2024-02-15 | GSE207687 | GEO
Project description:The Wnt/b-catenin signaling inhibits adipogenesis. Genome-wide profiling studies have revealed the enrichment of histone H3K27 methyltransferase PRC2 on Wnt genes. However, the functional significance of such a direct link between the two types of developmental regulators in mammalian cells, and the role of PRC2 in adipogenesis, remain unclear. Here we show PRC2 and its H3K27 methyltransferase activity are required for adipogenesis. PRC2 directly represses Wnt1, 6, 10a and 10b genes in preadipocytes and during adipogenesis. Deletion of the enzymatic Ezh2 subunit of PRC2 eliminates H3K27me3 on Wnt promoters and de-represses Wnt expression, which leads to activation of Wnt/b-catenin signaling and inhibition of adipogenesis. Ectopic expression of the wild type Ezh2, but not the enzymatically inactive F667I mutant, prevents the loss of H3K27me3 and the defects in adipogenesis in Ezh2-/- preadipocytes. The adipogenesis defects in Ezh2-/- cells can be rescued by expression of adipogenic transcription factors PPARa, C/EBPb, or inhibitors of Wnt/b-catenin signaling. Interestingly, Ezh2-/- cells show marked increase of H3K27 acetylation globally as well as on Wnt promoters. These results indicate that H3K27 methyltransferase PRC2 directly represses Wnt genes to facilitate adipogenesis, and suggest that acetylation and trimethylation on H3K27 play opposing roles in regulating Wnt expression. To identify additional PRC2-regulated genes in preadipocytes, we performed microarray analysis in Ezh2flox/flox preadipocytes infected with retroviruses expressing Cre or vector alone.
2010-03-19 | E-GEOD-20054 | biostudies-arrayexpress
Project description:The main goal of our study is to identify the molecular events that determine the gonadal identity in mammals. Although testis and ovary arise from a common embryonic primordium, they represent outcomes of opposing fate determination. This decision to differentiate into a testis or an ovary hinges upon the balance between two antagonizing factors, pro-testis SOX9 and pro-ovary β-catenin. This microarray analysis led to the identification of the genes involved in the fate of XX and XY gonads in absence of SOX9 and beta-catenin We developed mouse genetic models that lack either Sox9, β-catenin, or both specifically in the somatic cells. All embryos used in this study resulted from the crossing between Ctnnb1f/f; Sox9f/f females with Sf1-cre+/Tg ; Ctnnb1+/f; Sox9+/f males. XX and XY fetal gonads were collected at embryonic day E14.5
2015-05-26 | E-GEOD-67463 | biostudies-arrayexpress
Project description:The main goal of our study is to identify the molecular events that determine the gonadal identity in mammals. Although testis and ovary arise from a common embryonic primordium, they represent outcomes of opposing fate determination. This decision to differentiate into a testis or an ovary hinges upon the balance between two antagonizing factors, pro-testis SOX9 and pro-ovary β-catenin. This microarray analysis led to the identification of the genes involved in the fate of XX and XY gonads in absence of SOX9 and beta-catenin
2015-05-26 | GSE67463 | GEO
Project description:In summary, our study demonstrated the methylation sites of SFRP1 gene promoter in patients with colorectal cancer and adenoma and found SFRP1_16_17_18 CpG site was good performance as a diagnostic marker of colorectal cancer.
| 2401959 | ecrin-mdr-crc
Project description:• Atypical hyperplasias (AH) provide insights into early changes that may predispose breast epithelial cells to oncogenic transformation. • Of genes associated with premalignancy in prior studies, only mRNA levels of ESR1 and SFRP1 were detected in the present study. • Transcriptional profiling defined signatures distinguishing atypical hyperplasias. The patterns of expression were similar among hyperplastic lesions of lobular and ductal phenotype suggesting a common set of alterations underlying both lesions. Pathway analyses identified elevated expression of estrogen receptor alpha, androgen receptor and EGFR receptors and Rho signaling as central events nodes in the pathways altered in AH. • A set of 43 genes were identified as common targets using 2 different algorithms to detect signatures associated with AH. Knockdown of SFRP1 in a TERT immortalized breast epithelial cell line resulted in 14 genes from this signature being either up-regulated or down-regulated as observed in the expression profiles from AH. • The results demonstrate a signature of genes representing alterations that are common to the development of hyperplasias in both ductal and lobular epithelium. Loss of SFRP1 expression is a key player underlying the transcriptional changes in AH that directs a module of genes that can be used to improve reproducibility of diagnosis of AH.
2020-04-10 | GSE118432 | GEO