A5025272635- Acute Myeloid Leukemia Research
- Retinoids in leukemia and cellular processes
- Protein Degradation and Inhibitors
- Neurogenesis and neuroplasticity mechanisms
- Epigenetics and DNA Methylation
- MicroRNA in disease regulation
- Genomics and Chromatin Dynamics
- Immune Cell Function and Interaction
- Glioma Diagnosis and Treatment
- Histone Deacetylase Inhibitors Research
- Renal Diseases and Glomerulopathies
- Yeasts and Rust Fungi Studies
- DNA Repair Mechanisms
- T-cell and B-cell Immunology
- Fungal and yeast genetics research
- Telomeres, Telomerase, and Senescence
- Family and Disability Support Research
- Heat shock proteins research
- Autoimmune Bullous Skin Diseases
- Cancer and biochemical research
- Prostate Cancer Treatment and Research
- Cancer Research and Treatment
- Adipokines, Inflammation, and Metabolic Diseases
- Pluripotent Stem Cells Research
- Immunodeficiency and Autoimmune Disorders
Inserm
2015-2025
Aix-Marseille Université
2013-2025
Centre National de la Recherche Scientifique
2011-2025
Centre de Recherche en Cancérologie de Marseille
2019-2025
Institut Paoli-Calmettes
2018-2024
AOL (United States)
2023
Institut Pprime
2022
Paris Cardiovascular Research Center
2015-2017
Institut de Biologie du Développement Marseille
2011-2013
The success and limitations of current immunotherapies have pushed research toward the development alternative approaches possibility to manipulate other cytotoxic immune cells such as natural killer (NK) cells. Here, we targeted an intracellular inhibiting protein 'cytokine inducible SH2-containing protein' (CISH) in NK evaluate impact on their functions antitumor properties.To further understand CISH cells, developed a conditional Cish-deficient mouse model (Cishfl/flNcr1Ki/+ ). cytokine...
Meiotic recombination shows broad variations across species and along chromosomes is often suppressed at around genomic regions determining sexual compatibility such as mating type loci in fungi. Here, we show that the absence of Spo11-DSBs meiotic on Lakl0C-left, chromosome arm containing sex locus Lachancea kluyveri budding yeast, results from recruitment two axis proteins Red1 Hop1, essential for proper formation. Furthermore, cytological observation spread pachytene reveals Lakl0C-left...
Understanding the signals that control migration of neural progenitor cells in adult brain may provide new therapeutic opportunities. Reelin is best known for its role regulating cell during development, but we now demonstrate a novel function reelin injured brain. First, show upregulated around lesions. Second, experimentally increasing expression levels healthy mouse leads to change migratory behavior subventricular zone-derived progenitors, triggering them leave rostral stream (RMS) which...
Crescentic rapidly progressive glomerulonephritis (RPGN) represents the most aggressive form of acquired glomerular disease. While therapeutic approaches involve potentially toxic immunosuppressive strategies, pathophysiology remains incompletely understood. Podocytes are epithelial cells that normally growth-arrested because expression cyclin-dependent kinase (CDK) inhibitors. An exception is in RPGN where podocytes undergo a deregulation their differentiated phenotype and proliferate. Here...
Ciliary neurotrophic factor (CNTF) has been shown to be expressed after brain lesions and in particular demyelination. Here, we addressed the role of this cytokine regulation neural progenitor migration adult rodent brain. Using an acute model demyelination, show that CNTF is strongly re-expressed lesion involved postlesional mobilization endogenous progenitors participate myelin regenerative process. We controls subventricular zone (SVZ)-derived toward demyelinated corpus callosum....
Abstract Obesity is linked to limited adipose tissue (AT) remodeling capacity, leading hypertrophic adipocytes, senescence, and inflammation. We used a mouse model expressing mTert (p21 +/Tert ) from the Cdkn1a locus investigate role of mTERT in obesity-induced metabolic disorders. Conditional expression reduces disorders associated with obesity. In AT, this accompanied by decrease number senescent p21-positive cells, very short telomeres, oxidative DNA damage. Single nucleus RNA-seq data...
The transcription factor PLZF (promyelocytic leukemia zinc finger protein) acts as an epigenetic regulator balancing self-renewal and differentiation of hematopoietic cells through binding to various chromatin-modifying factors. First described a transcriptional repressor, is also associated with active transcription, although the molecular bases underlying differences are unknown. Here, we reveal that in cell line, predominantly transcribed genes. Additionally, identify new association...
Cancer cell heterogeneity is a major driver of therapy resistance. To characterize resistant cells and their vulnerabilities, we studied the PLZF-RARA variant acute promyelocytic leukemia, to retinoic acid (RA), using single-cell multiomics. We uncovered transcriptional chromatin in leukemia cells. identified subset RA with proliferation, DNA replication, repair signatures that depend on fine-tuned E2F network targeting epigenetic regulator enhancer zeste homolog 2 (EZH2). Epigenomic...
Disease progression and therapeutic resistance of prostate cancer (PC) are linked to multiple molecular events that promote survival plasticity. We previously showed heat shock protein 27 (HSP27) acted as a driver castration-resistant phenotype (CRPC) developed an oligonucleotides antisense (ASO) against HSP27 with evidence anti-cancer activity in men CRPC. Here, we show the tumor suppressor Menin (MEN1) is highly regulated by HSP27. overexpressed high-grade PC High MEN1 mRNA expression...
PLZF (promyelocytic leukemia zinc finger) is a transcription factor acting as global regulator of hematopoietic commitment. displays an epigenetic specificity by recruiting chromatin-modifying factors but little known about its role in remodeling chromatin cells committed toward given specific lineage. In murine myeloid progenitors, we decipher new for restraining active genes and enhancers targeting acetylated lysine 27 Histone H3 (H3K27ac). Functional analyses reveal that bound are...
The epigenetic machinery is frequently altered in acute myeloid leukemia. Focusing on cytogenetically normal (CN) AML, we previously described an abnormal H3K27me3 enrichment covering 70 kb the HIST1 cluster (6.p22) CN-AML patient blasts. Here, further investigate molecular, functional, and prognosis significance of this alteration named NPM1-mutated (NPM1mut) CN-AML. We found that three quarter NPM1mut patients were HIST1high. HIST1high group was associated with a favorable outcome...
Mutation of the TET2 DNA-hydroxymethylase has been associated with a number immune pathologies. The disparity in phenotype and clinical presentation among these pathologies leads to questions regarding role mutation promoting disease evolution different cell types. Here we show that, primary mast cells, Tet2 expression is induced response chronic acute activation signals. In TET2-deficient via oncogenic KITD816V allele mastocytosis, selects for specific epigenetic signature characterized by...
Abstract Meiotic recombination shows broad variations across species and along chromosomes, is often suppressed at around genomic regions determining sexual compatibility such as mating type loci in fungi. Here we show that the absence of Spo11-DSBs meiotic on Lakl0C-left, chromosome arm containing sex locus Lachancea kluyveri budding yeast, results from recruitment two axis proteins Red1 Hop1, essential for proper formation. Furthermore, cytological observation spread pachytene chromosomes...
ABSTRACT Cytogenetic normal AML with NPM1 mutations forms a distinct entity, associated an intermediate prognosis and heterogeneous response to treatment. We previously described epigenetic biomarker, defined by the level of H3K27me3 on 70kb HIST1 cluster in patient blast DNA. This mark separates cytogenetically mut into two groups patients differing their survival rate following chemotherapy. To better characterize influence biomarker disease progression, we performed transcriptomic histone...
SVZ-derived progenitors grown as neurospheres is a well-known model to study neural stem cell and progenitor functions such proliferation, differentiation/self-renewal, migration (Durbec Rougon, 2001). This protocol for preparing culture of from 8 early postnatal mouse brains (P0 P3). One week after plating, we can observe round floating neurospheres, each resulting the clonal expansion single EGF/FGF responsive progenitor.,...
Abstract Cytokine inducible SH2-containing protein (CISH) is a natural killer (NK) cell negative regulator of cytokine signaling pathway. To further understand CISH functions in NK cells, we developed conditional Cish -deficient mouse model cells ( fl/fl Ncr1 Ki/+ ). We detected no developmental or homeostatic difference cells. However, global gene expression compared to +/+ revealed upregulation pathways and genes associated with cycling activation. show that does not only regulate...
ABSTRACT PLZF (promyelocytic leukemia zinc finger) is a transcription factor acting as global regulator of hematopoietic commitment. displays an epigenetic specificity by recruiting chromatin-modifying factors but little known about its role in remodeling chromatin cells committed towards given specific lineage. In murine myeloid progenitors, we decipher new for restraining active genes and enhancers targeting acetylated lysine 27 Histone H3 (H3K27ac). Functional analyses reveal that bound...
Figure S1. Related to Fig. 2: Heatmap of the H3K27me3 level in a new cohort 78 NPM1mut CN-AML patients. S2. Analysis HIST1 status CD34low and CD34high sorted blasts. S3 4. Representative Integrative Genomics Viewer (IGV) tracks signal obtained from ChIP-chip data published Tiberi et al., 2015 S4. 5: Histone protein extraction S5. 5:Total abundance each histone types determined by IBAQ label-free quantification method. S6 related 6. Effect H1-3 KD on H1 subtype mRNA expression. Figure S7 H1d...
Table S1. Clinical and molecular characteristics in the GOELAMS Cohort (n = 46) according to H3K27me3 HIST1 status. S2. Multivariate analyses validation CN-AML cohort (n = 46). S3. Univariate Analyses for 3-HIST1-mRNA signature TCGA Metzeler cohorts. S4. of NPM1mut patients selected transcriptomic analysis.