A5024575058- Trace Elements in Health
- Acute Myeloid Leukemia Research
- Single-cell and spatial transcriptomics
- Iron Metabolism and Disorders
- Immune cells in cancer
- Cancer Genomics and Diagnostics
- Retinoids in leukemia and cellular processes
- Virus-based gene therapy research
- Protein Degradation and Inhibitors
- Cell death mechanisms and regulation
- Epigenetics and DNA Methylation
- Histone Deacetylase Inhibitors Research
- RNA regulation and disease
- Genomics and Chromatin Dynamics
- Hematopoietic Stem Cell Transplantation
- Autophagy in Disease and Therapy
- Advanced biosensing and bioanalysis techniques
- T-cell and B-cell Immunology
- Protease and Inhibitor Mechanisms
- Spectroscopy Techniques in Biomedical and Chemical Research
- Cancer-related gene regulation
- ATP Synthase and ATPases Research
- Gene Regulatory Network Analysis
- Peptidase Inhibition and Analysis
- CRISPR and Genetic Engineering
Inserm
2016-2024
Aix-Marseille Université
2016-2024
Centre National de la Recherche Scientifique
2011-2024
Centre de Recherche en Cancérologie de Marseille
2016-2024
Institut Paoli-Calmettes
2016-2023
Chiba University
2018-2023
La Ligue Contre le Cancer
2022
Université de Reims Champagne-Ardenne
2011-2013
Abstract Background Hematopoietic stem cells (HSCs) are the guarantor of proper functioning hematopoiesis due to their incredible diversity potential. During aging, heterogeneity HSCs changes, contributing deterioration immune system. In this study, we revisited mouse HSC compartment and its transcriptional plasticity during aging at unicellular scale. Results Through analysis 15,000 young aged transcriptomes, identified 15 groups revealing rare new specific abilities that change with age....
Cancer cell metabolism is increasingly recognized as providing an exciting therapeutic opportunity. However, a drug that directly couples targeting of metabolic dependency with the induction death in cancer cells has largely remained elusive. Here we report drug-like small-molecule ironomycin reduces mitochondrial iron load, resulting potent disruption metabolism. Ironomycin promotes recruitment and activation BAX/BAK, but outer membrane permeabilization (MOMP) does not lead to apoptotic...
Hematopoietic stem cell (HSC) aging is a multifactorial event leading to changes in HSC properties and functions, which are intrinsically coordinated affect the early hematopoiesis. To better understand mechanisms factors controlling these changes, we developed an original strategy construct Boolean model of differentiation. Based on our previous scRNA-seq data, exhaustively characterized active transcription modules or regulons along differentiation trajectory constructed influence graph...
Although originally described as transcriptional activator, SPI1/PU.1, a major player in haematopoiesis whose alterations are associated with haematological malignancies, has the ability to repress transcription. Here, we investigated mechanisms underlying gene repression erythroid lineage, which SPI1 exerts an oncogenic function by blocking differentiation. We show that represses genes binding active enhancers located intergenic or body regions. HDAC1 acts cooperative mediator of...
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...
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...
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...
Aims: Classical biochemical and molecular methods for discerning cells with epigenetic modifications are often biologically perturbing or even destructive. We wondered whether the noninvasive laser tweezer Raman spectroscopy technique allowed discrimination of single living human undergoing modifications. Materials & methods: Human Jurkat leukemic were treated inhibitors histone deacetylases (trichostatin A MS-275). Epigenetic changes monitored through electrophoresis, nuclear image...
Abstract Autophagy is an essential cellular process that maintains homeostasis by recycling damaged organelles and nutrients during development stress. ZKSCAN3 the sole identified master transcriptional repressor of autophagy in human cell lines. How achieves repression at mechanistic or organismal level however still remains to be elucidated. Furthermore, Zkscan3 knockout mice display no discernable autophagy-related phenotypes, suggesting there may substantial differences regulation...
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...
In diseases such as cancer, cells need to degrade the extracellular matrix (ECM) and therefore require high protease levels. Thus, aberrant tissue degradation is associated metalloproteinases (MMPs) overexpression resulting from different mechanisms including epigenetic events. One of most characterized DNA methylation causing changes in chromatin conformation, thereby decreasing accessibility transcriptional machinery a robust gene silencing. Modulation by hypomethylating agents...
Significance Reactive oxygen species (ROS) play a role in signaling immune cells, particular B cell activation and terminal differentiation secondary lymphoid organs. Nevertheless, their development the bone marrow (BM) still remains poorly explored. TP53INP1 is target of tumor suppressor p53, which mediates its antioxidant activity. We report surprising observation that chronic oxidative stress TP53INP1-deficient mice rescues lymphopoiesis BM during aging. ROS sustain IL-7R aged through...
Abstract Objective Chromatin texture patterns of tumour cell nuclei can serve as cancer biomarkers, either to define diagnostic classifications or obtain relevant prognostic information, in a large number human tumours. Epigenetic mechanisms, mainly DNA methylation and histone post‐translational modification, have been shown influence chromatin packing states, therefore nuclear texture. The aim this study was analyse effects these two mechanisms on texture, also correlation with gelatinase...
The matrix metalloproteinase (MMP) family members play an important role in various physiological and pathological processes. Although MMP-1 (collagenase-1) has been shown to be involved tumor invasiveness, the regulation of its expression is still not fully elucidated could implicate epigenetic mechanisms. aim this study was analyze effects Histone Deacetylase Inhibitor (HDI) trichostatin A (TSA) inhibitor DNA methylation 5-aza-2'-deoxycytidine (5-azadC) on proMMP-1 human HT1080...
Acute Promyelocytic Leukaemia (APL) arises from an aberrant chromosomal translocation involving the Retinoic Acid Receptor Alpha (RARA) gene, predominantly with (PML) or Zinc Finger (PLZF) genes. The resulting oncoproteins block haematopoietic differentiation program promoting proliferative promyelocytes. (RA) therapy is successful in most of PML::RARA patients, while PLZF::RARA patients frequently become resistant and relapse. Recent studies pointed to various underlying molecular...
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...
Abstract Autophagy is an essential cellular process that maintains homeostasis by recycling damaged organelles and nutrients during development stress. ZKSCAN3 the sole identified master transcriptional repressor of autophagy in humans. How achieves repression at mechanistic or organismal level however still remains to be elucidated. Here, we demonstrate vertebrate Drosophila M1BP are functionally homologous transcription factors repression. Expression prevents premature onset due loss...
ABSTRACT Hematopoietic stem cells (HSCs) are the guarantor of proper functioning hematopoiesis due to their incredible diversity potential. During aging heterogeneity mouse HSCs evolves, which contributes deterioration immune system. Here we address transcriptional plasticity HSC upon at single-cell resolution. Through analysis 15,000 young and aged transcriptomes, reveal 15 clusters unveiling rare specific abilities that change with age. Pseudotime ordering complemented regulon showed...
Abstract Hematopoietic stem cell (HSC) aging is a multifactorial event that leads to changes in HSC properties and function. These are intrinsically coordinated affect the early hematopoiesis, involving hematopoietic progenitor cells (HSPCs). The objective of this work better understand mechanisms factors controlling these changes. We have therefore developed an original strategy construct Boolean network genes explaining priming homeostasis HSCs (graphical abstract) . Based on our previous...