A5075594149- Hematopoietic Stem Cell Transplantation
- Acute Myeloid Leukemia Research
- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Chronic Myeloid Leukemia Treatments
- Immunotherapy and Immune Responses
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Effects of Radiation Exposure
- Immune cells in cancer
- Epigenetics and DNA Methylation
- Acute Lymphoblastic Leukemia research
- RNA modifications and cancer
- Immune Response and Inflammation
- Cancer-related gene regulation
- Cell Adhesion Molecules Research
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Childhood Cancer Survivors' Quality of Life
- Mesenchymal stem cell research
- DNA Repair Mechanisms
- Cancer, Hypoxia, and Metabolism
- Protein Degradation and Inhibitors
- PI3K/AKT/mTOR signaling in cancer
- Phagocytosis and Immune Regulation
- Retinoids in leukemia and cellular processes
- Renal and related cancers
Inserm
2015-2025
Institut Gustave Roussy
2024-2025
Université Paris Cité
2007-2023
Commissariat à l'Énergie Atomique et aux Énergies Alternatives
2015-2023
La Ligue Contre le Cancer
2016-2023
Université Paris-Saclay
2015-2023
CEA Paris-Saclay - Etablissement de Fontenay-aux-roses
2015-2023
CEA Paris-Saclay
2015-2023
Acute Leukemia French Association
2023
Université Côte d'Azur
2021-2023
Human acute T-cell lymphoblastic leukemias and lymphomas (T-ALL) are commonly associated with gain-of-function mutations in Notch1 that contribute to T-ALL induction maintenance. Starting from an expression-profiling screen, we identified c-myc as a direct target of Notch-dependent cell lines, which Notch accounts for the majority expression. In functional assays, inhibitors interfere progrowth effects activated Notch1, enforced expression rescues multiple Notch1-dependent lines withdrawal....
Notch1 (N1) receptor signaling is essential and sufficient for T cell development, recently developed in vitro culture systems point to members of the Delta family as being physiological N1 ligands. We explored ability Delta1 (DL1) DL4 induce lineage commitment and/or maturation vivo from bone marrow (BM) precursors conditionally gene targeted N2. In DL1 can trigger via either or N1- N2-mediated also occur spleen after short-term BM transplantation. However, N2–DL1–mediated does not allow...
Abstract How transcription factors (TFs) cooperate within large protein complexes to allow rapid modulation of gene expression during development is still largely unknown. Here we show that the key haematopoietic LIM-domain-binding protein-1 (LDB1) TF complex contains several activator and repressor components together maintain an erythroid-specific programme primed for activation until differentiation induced. A combination proteomics, functional genomics in vivo studies presented here...
Lymph node (LN) stromal cells provide survival signals and adhesive substrata to lymphocytes. During an immune response, B cell follicles enlarge, questioning how LN manage these cellular demands. Herein, we used a murine fate mapping system describe new type that resides in the T zone of resting LNs. We demonstrated upon inflammation, progressively trespassed into adjacent surrounded converted CXCL13 secreting return delineated boundaries growing follicle. Acute ablation inflamed LNs...
Abstract Genome-wide association studies (GWAS) have identified numerous genetic variants linked to human diseases, mostly located in non-coding regions of the genome, particularly putative enhancers. However, functional assessment GWAS has progressed at slow pace, since functions vast majority genomic enhancers not been defined, impeding interpretation disease-susceptibility variants. The HBS1L-MYB intergenic region harbors multiple SNPs associated with clinical erythroid parameters,...
Genome-wide association studies (GWAS) have identified numerous genetic variants linked to human diseases, mostly located in non-coding regions of the genome, particularly putative enhancers. However, functional assessment GWAS has progressed at slow pace, since functions vast majority genomic enhancers not been defined, impeding interpretation disease-susceptibility variants. The HBS1L-MYB intergenic region harbors multiple SNPs associated with clinical erythroid parameters, including fetal...
Fusion oncogenes are prevalent in several pediatric cancers, yet little is known about the specific associations between age and phenotype. We observed that fusion oncogenes, such as ETO2-GLIS2, associated with acute megakaryoblastic or other myeloid leukemia subtypes an age-dependent manner. Analysis of a novel inducible transgenic mouse model showed ETO2-GLIS2 expression fetal hematopoietic stem cells induced rapid whereas adult bone marrow resulted shift toward transformation strikingly...
Metastasis is a major clinical issue and results in poor prognosis for most cancers. The Junctional Adhesion Molecule‐C (JAM‐C) expressed by B16 melanoma endothelial cells has been involved metastasis of tumor through homophilic JAM‐C/JAM‐C trans‐interactions. Here, we show that JAM‐B contributes to murine its interaction with JAM‐C on cells. We further this adhesion molecular pair mediates cell primary Lung Microvascular Endothelial Cells it functional vivo as demonstrated the reduced Jam‐b...
Abstract The junctional adhesion molecules Jam-b and Jam-c interact together at interendothelial junctions have been involved in the regulation of immune response, inflammation, leukocyte migration. More recently, has found to be expressed by hematopoietic stem progenitor cells (HSPC) mouse. Conversely, we reported that is present on bone marrow stromal Jam-b-deficient mice defects cell pool. In this study, addressed whether interaction between participates HSPC mobilization or...
Hypoxia plays a major role in the physiology of hematopoietic and immune niches. Important clues from works mouse have paved way to investigate low O2 levels hematopoiesis. However, whether hypoxia impacts initial steps human lymphopoiesis remains unexplored. Here, we show that regulates cellular metabolic profiles umbilical cord blood (UCB)-derived progenitor cells. more specifically enhances vitro lymphoid differentiation potentials lymphoid-primed multipotent progenitors (LMPPs)...
Hematopoietic stem cells are responsible for life-long blood cell production and highly sensitive to exogenous stresses. The effects of low doses ionizing radiations on radiosensitive tissues such as the hematopoietic tissue still unknown despite their increasing use in medical imaging. Here, we study consequences differentiation self-renewal capacities human primary stem/progenitor (HSPC). We found that a single 20 mGy dose impairs reconstitution potential HSPC but not properties. In...
Abstract Resistance to chemotherapy, a major therapeutic challenge in the treatment of T-cell acute lymphoblastic leukemia (T-ALL), can be driven by interactions between leukemic cells and microenvironment that promote survival cells. The bone marrow, an important niche, has low oxygen partial pressures highly participate regulation normal hematopoiesis. Here we show hypoxia inhibits T-ALL cell growth slowing down cycle progression, decreasing mitochondria activity, increasing glycolysis,...
Hematopoietic stem/progenitor cells (HSPCs) are regulated through numerous molecular mechanisms that have not been interconnected. The transcription factor stem cell leukemia/T-cell acute leukemia 1 (TAL1) controls human HSPC but its mechanism of action is clarified. In this study, we show knockdown (KD) or short-term conditional over-expression (OE) TAL1 in ex vivo, respectively, blocks and maintains hematopoietic potentials, affecting proliferation HSPC. Comparative gene expression...
Abstract Hematopoietic stem cells (HSCs) located in adult bone marrow or fetal liver mammals produce all from the blood system. At top of hierarchy are long-term HSCs endowed with lifelong self-renewal and differentiation properties. These features controlled through key microenvironmental cues regulatory pathways, such as Wnt signaling. We showed previously that PTK7, a tyrosine kinase receptor involved planar cell polarity, plays role epithelial signaling; however, its function...
Abstract The role of the thymus in T cell commitment hemopoietic precursor is yet controversial. We previously identified a major progenitor activity cells isolated from bone marrow-derived spleen colonies. In this study, we characterize properties these pre-T cells. demonstrate that they have unique phenotype and can be generated total absence any thymic influence. Indeed, even when studied at single-cell level, extrathymic cell-committed precursors express cell-specific genes. Moreover,...
Common lymphoid progenitors (CLP) are generated in adult bone marrow (BM), but the intermediate steps leading to T cell commitment unknown, and so is site at which this occurs. Here, we show that colonies arising spleen 12 days after BM injection harbor precursors undetectable BM. These did not generate myeloid cells vivo repopulated thymus peripheral compartment much faster than CLP. Two lineage negative (Lin−) subpopulations were distinguished, namely CD44+ Thy1− still capable of natural...
Abstract Dok1 and Dok2 proteins play a crucial role in myeloid cell proliferation as demonstrated by gene inactivation, which induces myeloproliferative disease aging mice. In this study, we show that Dok1/Dok2 deficiency affects myeloproliferation even at young age. An increase the cellularity of multipotent progenitors is observed Dok1/Dok2-deficient This associated with an cells undergoing cycle, restricted to committed progenitors. Furthermore, cellular stress triggered 5-fluorouracil...
Abstract The development and maintenance of secondary lymphoid organs, such as lymph nodes, occur in a highly coordinated manner involving chemokine production by stromal cells. Although developmental pathways inducing during organogenesis are known, signals maintaining cytokine adults still elusive. In this study, we show that thrombomodulin platelet-derived growth factor receptor α identify population fibroblastic reticular cells which secretion is controlled JAM-C. We demonstrate...