Leukemic initiation in Jam-C-deficient HSPC reveals AP-1/TNF- gene expression signature as a biomarker for AML
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA986914 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR25010018_1.fastq.gz | Fastqsanger.gz | |||
| SRR25010018_2.fastq.gz | Fastqsanger.gz | |||
| SRR25010019_1.fastq.gz | Fastqsanger.gz | |||
| SRR25010019_2.fastq.gz | Fastqsanger.gz | |||
| SRR25010020_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 24 |
Similar Datasets
Project description:The leukemic stem cell score 17 (LSC-17) based on stemness gene expression signature is recognized as indicator of poor disease outcome in acute myeloid leukemia (AML). However, our understanding of the relationships between LSC and pre-leukemic cells is still incomplete. In particular, it is not known whether “niche-anchoring” of pre-leukemic cell affects disease evolution. To address this issue, we conditionally inactivated the adhesion molecule Jam-C expressed by haematopoietic stem cells (HSC) and LSC in an inducible iMLL-AF9-driven AML mouse model. Deletion of Jam-C in HSC before activation of the leukemia-initiating iMLL-AF9 fusion resulted in a shift from long term (LT-HSC) to short term-HSC (ST-HSC) expansion, suggesting that transcriptional programs of leukemic HSC were altered. RNA sequencing performed on leukemic HSC and GMP isolated from diseased mice revealed that genes upregulated in Jam-C-deficient animals belonged to Activation Protein-1 (AP-1) and TNF-/NFB signalling pathways. Using three publicly available datasets of AML gene expression, we further showed that human orthologs of dysregulated genes belonged to a gene regulon distinct from the LSC-17 signature. A prognosis 14-genes score from the AP-1/TNF-/NFB gene expression signature was established and called ATIC for “AP-1/TNF- initiating cell”. ATIC was independent of the LSC-17 score and improved the stratification of AML patients obtained with the LSC-17 score suggesting that the ATIC score reflected the presence of ST-HSC-initiating AML cells at diagnosis. Collectively we provide a novel tool for understanding AML disease heterogeneity through the identification of specific transcriptional programs for leukemic stem and progenitor cells.
2024-07-01 | GSE235693 | GEO
Project description:Junction Adhesion Molecule-A (JAM-A) is present on leukocytes and platelets where it promotes cell adhesion and motility. We are interested in an interaction between JAM-A and tumor progression/metastases. To address this point, we mated JAM-A-/- mice and mouse mammary tumor model MMTV-PyMT mice which, which express polyoma middle T antigen under the control of mouse mammary tumor virus. MMTV-PyMT mice show 100% penetration of mammary tumor and highly metastases to lung. MMTV-PyMT mice without JAM-A show less primary tumor progression, therefore JAM-A enhance primary tumor progression. Then we are addressing the molecular mechanism of this phenomenon by in vivo. Furthermore, we would like to examine JAM-A deficient MMTV tumor signature.
2010-10-01 | GSE22555 | GEO
Project description:Junction Adhesion Molecule-A (JAM-A) is present on leukocytes and platelets where it promotes cell adhesion and motility. We are interested in an interaction between JAM-A and tumor progression/metastases. To address this point, we mated JAM-A-/- mice and mouse mammary tumor model MMTV-PyMT mice which, which express polyoma middle T antigen under the control of mouse mammary tumor virus. MMTV-PyMT mice show 100% penetration of mammary tumor and highly metastases to lung. MMTV-PyMT mice without JAM-A show less primary tumor progression, therefore JAM-A enhance primary tumor progression. Then we are addressing the molecular mechanism of this phenomenon by in vivo. Furthermore, we would like to examine JAM-A deficient MMTV tumor signature. Each 3 MMTV-PyMT JAm-A+/+ (JamA+) and 3 MMTV JAM-A-/- (JamA-) mammary tumor were resected at early stages of tumor development for RNA extraction and hybridization on Affymetrix microarrays.
2010-10-01 | E-GEOD-22555 | biostudies-arrayexpress
Project description:Pontibacter sp. JAM-7 Genome sequencing
| PRJNA1167886 | ENA
Project description:Hepatocytes are polarized epithelial cells whose function depends upon their ability to distinguish between the apical and basolateral surfaces that are located at intercellular tight junctions. It has been proposed that the signaling cascades that originate at these junctions influence cellular activity by controlling gene expression in the cell nucleus. To assess the validity of this proposal with regard to hepatocytes, we depleted expression of the tight junction protein junctional adhesion molecule-A (JAM-A) in the HepG2 human hepatocellular carcinoma cell line. Reduction of JAM-A resulted in a striking change in cell morphology, with cells forming single-layered sheets instead of the normal multi-layered clusters. In the absence of JAM-A, other tight junction proteins were mislocalized, and canaliculi, which form the apical face of the hepatocyte, were consequently absent. While most changes in gene expression were modest, there was a strong transcriptional induction of the adherens junction protein E-cadherin in cells with reduced levels of JAM-A. This increase in E-cadherin was partially responsible for the observed alterations in cell morphology and mislocalization of tight junction proteins. We therefore propose that we have uncovered a novel mechanism for crosstalk between specific components of tight and adherens junctions that can be utilized to regulate adhesion between hepatic cells and to maintain hepatocyte cell polarity. Keywords: HepG2 cells
2007-07-01 | GSE6080 | GEO
Project description:Endothelial cells form a barrier between the components present in the blood and the underlying tissue. Essential to formation of this barrier are junctional complexes present between cells. These complexes are dynamic, tightly regulated and remodel during key physiological processes such as inflammation, angiogenesis and development to allow passage of molecules, cells and movement of endothelial cells. One such junctional protein, Jam-C, is involved in the pathology of a number of inflammatory disease states and its inhibition in vitro and in vivo results in aberrant forms of leukocyte migration, dysregulated angiogenesis and inhibition of cell migration. Intracellular trafficking has been shown to be a general means of regulating the function of junctional proteins but its role in Jam-C function is unclear. Using a combination of receptor mutagenesis, HRP and APEX-2 proximity labelling alongside light and electron microscopy, we here characterise the dynamics and route of Jam-C trafficking. Rather than trafficking with junctional proteins associated with the inflammatory process, Jam-C co-traffics with receptors associated with changes in permeability such as VE-Cadherin, NRP-1 and 2. We show that Jam-C becomes ubiquitylated by the E-3 ligase CBL and that this post translational modification controls the likelihood of its degradation in the lysosomes or its recycling back to the cell surface. Finally, we show that Jam-C trafficking is essential for some of the endothelial functions of Jam-C.
2019-11-06 | PXD013003 | Pride
Project description:During pregnancy, trophoblasts in the placenta are important in the success of pregnancy. We identify an adhesion molucule, JAM-C, which expresses on membrane of column cytotrophoblasts and regulates the differentiation and migration of trophoblasts. Primary cytotrophoblasts isolated from 1st trimester villi were transfected with JAM-C or control plasmids. RNA-seq analysis was sujected to identify differentially expressed genes and pathways potentially altered.
2020-10-31 | GSE156258 | GEO
Project description:Hepatocytes are polarized epithelial cells whose function depends upon their ability to distinguish between the apical and basolateral surfaces that are located at intercellular tight junctions. It has been proposed that the signaling cascades that originate at these junctions influence cellular activity by controlling gene expression in the cell nucleus. To assess the validity of this proposal with regard to hepatocytes, we depleted expression of the tight junction protein junctional adhesion molecule-A (JAM-A) in the HepG2 human hepatocellular carcinoma cell line. Reduction of JAM-A resulted in a striking change in cell morphology, with cells forming single-layered sheets instead of the normal multi-layered clusters. In the absence of JAM-A, other tight junction proteins were mislocalized, and canaliculi, which form the apical face of the hepatocyte, were consequently absent. While most changes in gene expression were modest, there was a strong transcriptional induction of the adherens junction protein E-cadherin in cells with reduced levels of JAM-A. This increase in E-cadherin was partially responsible for the observed alterations in cell morphology and mislocalization of tight junction proteins. We therefore propose that we have uncovered a novel mechanism for crosstalk between specific components of tight and adherens junctions that can be utilized to regulate adhesion between hepatic cells and to maintain hepatocyte cell polarity. Experiment Overall Design: HepG2 cells were transduced with lentiviruses and stably selected using puromycin. Comparison of four controls and five JAM-A knockdown samples.
2008-06-14 | E-GEOD-6080 | biostudies-arrayexpress
Project description:Microcella alkaliphila JAM-AC0309 whole genome shotgun sequence
| PRJDB4439 | ENA