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138 results on '"Arcangeli, Marie-Laure"'

9. Architectural and functional heterogeneity of hematopoietic stem/progenitor cells in non-del(5q) myelodysplastic syndromes

Author

Chesnais, Virginie, Arcangeli, Marie-Laure, Delette, Caroline, Rousseau, Alice, Guermouche, Hélène, Lefevre, Carine, Bondu, Sabrina, Diop, M'boyba, Cheok, Meyling, Chapuis, Nicolas, Legros, Laurence, Raynaud, Sophie, Willems, Lise, Bouscary, Didier, Lauret, Evelyne, Bernard, Olivier A., Kosmider, Olivier, Pflumio, Françoise, and Fontenay, Michaela

Published
2017
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10. Supplementary Tables 1 to 11 from Ontogenic Changes in Hematopoietic Hierarchy Determine Pediatric Specificity and Disease Phenotype in Fusion Oncogene–Driven Myeloid Leukemia

Author

Lopez, Cécile K., primary, Noguera, Esteve, primary, Stavropoulou, Vaia, primary, Robert, Elie, primary, Aid, Zakia, primary, Ballerini, Paola, primary, Bilhou-Nabera, Chrystèle, primary, Lapillonne, Hélène, primary, Boudia, Fabien, primary, Thirant, Cécile, primary, Fagnan, Alexandre, primary, Arcangeli, Marie-Laure, primary, Kinston, Sarah J., primary, Diop, M'Boyba, primary, Job, Bastien, primary, Lecluse, Yann, primary, Brunet, Erika, primary, Babin, Loélia, primary, Villeval, Jean Luc, primary, Delabesse, Eric, primary, Peters, Antoine H.F.M., primary, Vainchenker, William, primary, Gaudry, Muriel, primary, Masetti, Riccardo, primary, Locatelli, Franco, primary, Malinge, Sébastien, primary, Nerlov, Claus, primary, Droin, Nathalie, primary, Lobry, Camille, primary, Godin, Isabelle, primary, Bernard, Olivier A., primary, Göttgens, Berthold, primary, Petit, Arnaud, primary, Pflumio, Françoise, primary, Schwaller, Juerg, primary, and Mercher, Thomas, primary

Published
2023
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11. Data from Ontogenic Changes in Hematopoietic Hierarchy Determine Pediatric Specificity and Disease Phenotype in Fusion Oncogene–Driven Myeloid Leukemia

Author

Lopez, Cécile K., primary, Noguera, Esteve, primary, Stavropoulou, Vaia, primary, Robert, Elie, primary, Aid, Zakia, primary, Ballerini, Paola, primary, Bilhou-Nabera, Chrystèle, primary, Lapillonne, Hélène, primary, Boudia, Fabien, primary, Thirant, Cécile, primary, Fagnan, Alexandre, primary, Arcangeli, Marie-Laure, primary, Kinston, Sarah J., primary, Diop, M'Boyba, primary, Job, Bastien, primary, Lecluse, Yann, primary, Brunet, Erika, primary, Babin, Loélia, primary, Villeval, Jean Luc, primary, Delabesse, Eric, primary, Peters, Antoine H.F.M., primary, Vainchenker, William, primary, Gaudry, Muriel, primary, Masetti, Riccardo, primary, Locatelli, Franco, primary, Malinge, Sébastien, primary, Nerlov, Claus, primary, Droin, Nathalie, primary, Lobry, Camille, primary, Godin, Isabelle, primary, Bernard, Olivier A., primary, Göttgens, Berthold, primary, Petit, Arnaud, primary, Pflumio, Françoise, primary, Schwaller, Juerg, primary, and Mercher, Thomas, primary

Published
2023
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12. Supplementary Figures and Legends from Ontogenic Changes in Hematopoietic Hierarchy Determine Pediatric Specificity and Disease Phenotype in Fusion Oncogene–Driven Myeloid Leukemia

Author

Lopez, Cécile K., primary, Noguera, Esteve, primary, Stavropoulou, Vaia, primary, Robert, Elie, primary, Aid, Zakia, primary, Ballerini, Paola, primary, Bilhou-Nabera, Chrystèle, primary, Lapillonne, Hélène, primary, Boudia, Fabien, primary, Thirant, Cécile, primary, Fagnan, Alexandre, primary, Arcangeli, Marie-Laure, primary, Kinston, Sarah J., primary, Diop, M'Boyba, primary, Job, Bastien, primary, Lecluse, Yann, primary, Brunet, Erika, primary, Babin, Loélia, primary, Villeval, Jean Luc, primary, Delabesse, Eric, primary, Peters, Antoine H.F.M., primary, Vainchenker, William, primary, Gaudry, Muriel, primary, Masetti, Riccardo, primary, Locatelli, Franco, primary, Malinge, Sébastien, primary, Nerlov, Claus, primary, Droin, Nathalie, primary, Lobry, Camille, primary, Godin, Isabelle, primary, Bernard, Olivier A., primary, Göttgens, Berthold, primary, Petit, Arnaud, primary, Pflumio, Françoise, primary, Schwaller, Juerg, primary, and Mercher, Thomas, primary

Published
2023
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13. From normal hematopoiesis to malignancies: Highlights from the 2021 Meeting of the Club Hematopoiesis and Oncogenesis

Author

Troadec, Marie-Bérengère, primary, Porteu, Françoise, additional, Arcangeli, Marie-Laure, additional, Foudi, Adlen, additional, Bluteau, Dominique, additional, De Sepulveda, Paulo, additional, Guillouf, Christel, additional, Mazure, Nathalie M., additional, Meggetto, Fabienne, additional, Brunet De La Grange, Philippe, additional, and Broccardo, Cyril, additional

Published
2023
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15. Molecular dynamics of myeloid progenitor transformation

Author

Arcangeli, Marie-Laure, Mazurier, Frédéric, Centre méditerranéen de médecine moléculaire (C3M), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), Institut de Génétique et Développement de Rennes (IGDR), and Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )

Subjects
[SDV.GEN]Life Sciences [q-bio]/Genetics
Abstract

International audience; Acute myeloid leukaemia (AML) is the most common acute leukaemia in adults. AML results from the accumulation of abnormal immature myeloid progenitors, also called blasts, that are blocked in their differentiation. AML is a very heterogeneous disease with more than a dozen of genetically distinct entities (See new AML classification from [1]). Each genetically distinct AML subgroup is generally defined by gene mutations and/or alterations related to its aggressiveness, and is associated to [...]

Published
2023
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16. Reprogramming monocyte-derived macrophages through caspase inhibition

Author

Chaintreuil, Paul, primary, Laplane, Lucie, additional, Esnault, Florian, additional, Ghesquier, Victoria, additional, Savy, Coline, additional, Furstoss, Nathan, additional, Arcangeli, Marie-Laure, additional, Cluzeau, Thomas, additional, Robert, Guillaume, additional, Droin, Nathalie, additional, Solary, Eric, additional, Auberger, Patrick, additional, and Jacquel, Arnaud, additional

Published
2021
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21. Ontogenic Changes in Hematopoietic Hierarchy Determine Pediatric Specificity and Disease Phenotype in Fusion Oncogene–Driven Myeloid Leukemia

Author

Lopez, Cécile K., primary, Noguera, Esteve, additional, Stavropoulou, Vaia, additional, Robert, Elie, additional, Aid, Zakia, additional, Ballerini, Paola, additional, Bilhou-Nabera, Chrystèle, additional, Lapillonne, Hélène, additional, Boudia, Fabien, additional, Thirant, Cécile, additional, Fagnan, Alexandre, additional, Arcangeli, Marie-Laure, additional, Kinston, Sarah J., additional, Diop, M'Boyba, additional, Job, Bastien, additional, Lecluse, Yann, additional, Brunet, Erika, additional, Babin, Loélia, additional, Villeval, Jean Luc, additional, Delabesse, Eric, additional, Peters, Antoine H.F.M., additional, Vainchenker, William, additional, Gaudry, Muriel, additional, Masetti, Riccardo, additional, Locatelli, Franco, additional, Malinge, Sébastien, additional, Nerlov, Claus, additional, Droin, Nathalie, additional, Lobry, Camille, additional, Godin, Isabelle, additional, Bernard, Olivier A., additional, Göttgens, Berthold, additional, Petit, Arnaud, additional, Pflumio, Françoise, additional, Schwaller, Juerg, additional, and Mercher, Thomas, additional

Published
2019
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22. Reprogramming monocyte-derived macrophages through caspase inhibition.

Author

Chaintreuil, Paul, Laplane, Lucie, Esnault, Florian, Ghesquier, Victoria, Savy, Coline, Furstoss, Nathan, Arcangeli, Marie-Laure, Cluzeau, Thomas, Robert, Guillaume, Droin, Nathalie, Solary, Eric, Auberger, Patrick, and Jacquel, Arnaud

Subjects
MACROPHAGES, CASPASES, APOPTOSIS, MORPHOGENESIS, HEMATOLOGIC malignancies
Abstract

Macrophages are widely distributed innate immune cells that play an indispensable role in a variety of physiologic and pathologic processes, including organ development, host defense, acute and chronic inflammation, solid and hematopoietic cancers. Beyond their inextricable role as conveyors of programmed cell death, we have previously highlighted that caspases exert non-apoptotic functions, especially during the differentiation of monocyte-derived cells in response to CSF-1. Here, we found that non-canonic cleavages of caspases, reflecting their activation, are maintained during IL-4-induced monocyte-derived macrophages polarization. Moreover, Emricasan, a pan-caspase inhibitor that demonstrated promising preclinical activity in various diseases and safely entered clinical testing for the treatment of liver failure, prevents the generation and the anti-inflammatory polarization of monocyte-derived macrophages ex vivo. Interestingly, caspase inhibition also triggered the reprogramming of monocytederived cells evidenced by RNA sequencing. Taken together, our findings position Emricasan as a potential alternative to current therapies for reprogramming macrophages in diseases driven by monocyte-derived macrophages. [ABSTRACT FROM AUTHOR]

Published
2022
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23. Hypoxia Regulates Lymphoid Development of Human Hematopoietic Progenitors

Author

Chabi, Sara, Uzan, Benjamin, Naguibneva, Irina, Rucci, Julien, Fahy, Lucine, Calvo, Julien, Arcangeli, Marie-Laure, Mazurier, Frédéric, Pflumio, Françoise, Haddad, Rima, CCSD, Accord Elsevier, Stabilité génétique, cellules souches et radiations (SGCSR (U_1274 / UMR_E_008)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Université Paris Cité (UPCité), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Université de Paris (UP)

Subjects
B-Lymphocytes, [SDV]Life Sciences [q-bio], Lymphopoiesis, Cell Differentiation, Lymphoid Progenitor Cells, Hematopoietic Stem Cells, Hypoxia-Inducible Factor 1, alpha Subunit, Cell Hypoxia, [SDV] Life Sciences [q-bio], Killer Cells, Natural, Oxygen, lcsh:Biology (General), Basic Helix-Loop-Helix Transcription Factors, Humans, lcsh:QH301-705.5, Cells, Cultured
Abstract

Summary: Hypoxia plays a major role in the physiology of hematopoietic and immune niches. Important clues from works in mouse have paved the way to investigate the role of low O2 levels in hematopoiesis. However, whether hypoxia impacts the initial steps of human lymphopoiesis remains unexplored. Here, we show that hypoxia regulates cellular and metabolic profiles of umbilical cord blood (UCB)-derived hematopoietic progenitor cells. Hypoxia more specifically enhances in vitro lymphoid differentiation potentials of lymphoid-primed multipotent progenitors (LMPPs) and pro-T/natural killer (NK) cells and in vivo B cell potential of LMPPs. In accordance, hypoxia exacerbates the lymphoid gene expression profile through hypoxia-inducible factor (HIF)-1α (for LMPPs) and HIF-2α (for pro-T/NK). Moreover, loss of HIF-1/2α expression seriously impedes NK and B cell production from LMPPs and pro-T/NK. Our study describes how hypoxia contributes to the lymphoid development of human progenitors and reveals the implication of the HIF pathway in LMPPs and pro-T/NK-cell lymphoid identities. : Chabi et al. show that low oxygen levels promote the development of human lymphoid cells from umbilical cord blood progenitors. The work also highlights how hypoxia-inducible factors, the major actors of hypoxia cell response, are involved in the early steps of human lymphopoiesis by supporting cell differentiation and production.

Published
2019
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24. Human hematopoietic stem/progenitor cells display reactive oxygen species-dependent long-term hematopoietic defects after exposure to low doses of ionizing radiations

Author

Henry, Elia, primary, Souissi-Sahraoui, Inès, additional, Deynoux, Margaux, additional, Lefèvre, Andréas, additional, Barroca, Vilma, additional, Campalans, Anna, additional, Ménard, Véronique, additional, Calvo, Julien, additional, Pflumio, Françoise, additional, and Arcangeli, Marie-Laure, additional

Published
2019
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26. Bone marrow sites differently imprint dormancy and chemoresistance to T-cell acute lymphoblastic leukemia

Author

Cahu, Xavier, Calvo, Julien, Poglio, Sandrine, Prade, Nais, Colsch, Benoit, Arcangeli, Marie-Laure, Leblanc, Thierry, Petit, Arnaud, Baleydier, Frederic, Baruchel, André, Landman-Parker, Judith, Junot, Christophe, Larghero, Jérome, Ballerini, Paola, Delabesse, Eric, Uzan, Benjamin, Pflumio, Françoise, Institut de Radiobiologie Cellulaire et Moléculaire (IRCM), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Université Paris-Sud - Paris 11 (UP11), Centre de Recherches en Cancérologie de Toulouse (CRCT), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Recherche Agronomique (INRA), Université Paris Saclay (COmUE), AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Trousseau [APHP], Hôpital de l'Hôtel-Dieu de Lyon, Partenaires INRAE, CIC - Biotherapie - Saint Louis ((CIC-BT 301)), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], INSERM, CEA, Universite Paris Diderot, Universite Paris Sud, Institut National du Cancer (INCA), Canceropole d'Ile de France, Region Ile de France, Ligue Nationale contre le Cancer (LNCC, equipe labellisee), Association Laurette Fugain, Fondation de France, Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)

Subjects
Lymphoid Neoplasia, [SDV]Life Sciences [q-bio]
Abstract

International audience; T-cell acute lymphoblastic leukemia (T-ALL) expands in various bonemarrow (BM) sites of the body. We investigated whether different BM sites could differently modulate T-ALL propagation using in vivo animal models. We observed that mouse and human T-ALL develop slowly in the BM of tail vertebrae compared with the BM from thorax vertebrae. T-ALL recovered from tail BM displays lower cell-surfacemarker expression and decreased metabolism and cell-cycle progression, demonstrating a dormancy phenotype. Functionally, tailderived T-ALL exhibit a deficient short-term ex vivo growth and a delayed in vivo propagation. These features are noncell-autonomous because T-ALL fromtail and thorax shares identical genomic abnormalities and functional disparities disappear in vivo and in prolonged in vitro assays. Importantly tail-derived T-ALL displays higher intrinsic resistance to cell-cycle-related drugs (ie, vincristine sulfate and cytarabine). Of note, T-ALL recovered from gonadal adipose tissues or from cocultures with adipocytes shares metabolic, cell-cycle, and phenotypic or chemoresistance features, with tail-derived T-ALL suggesting adipocytes may participate in the tail BM imprints on T-ALL. Altogether these results demonstrate that BM sites differentially orchestrate T-ALL propagation stamping specific features to leukemic cells such as quiescence and decreased response to cell-cycle-dependent chemotherapy.

Published
2017
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27. Bone marrow sites differently imprint dormancy and chemoresistance to T-cell acute lymphoblastic leukemia

Author

Poglio, Sandrine, Prade, Nais, Colsch, Benoît, Arcangeli, Marie-Laure, Leblanc, Thierry, Petit, Arnaud, Baleydier, Frédéric, Baruchel, André, Landman-Parker, Judith, Junot, Christophe, Larghero, Jérôme, Ballerini, Paola, Delabesse, Eric, Uzan, Benjamin, Cahu, Xavier, Calvo, Julien, and Pflumio, Françoise

Subjects
moelle osseuse, transformation lymphoblastique, quiescence, leucemie, dormance, cycle cellulaire, chimiorésistance
Abstract

T-cell acute lymphoblastic leukemia (T-ALL) expands in various bonemarrow (BM) sites of the body. We investigated whether different BM sites could differently modulate T-ALL propagation using in vivo animal models. We observed that mouse and human T-ALL develop slowly in the BM of tail vertebrae compared with the BM from thorax vertebrae. T-ALL recovered from tail BM displays lower cell-surfacemarker expression and decreased metabolism and cell-cycle progression, demonstrating a dormancy phenotype. Functionally, tailderived T-ALL exhibit a deficient short-term ex vivo growth and a delayed in vivo propagation. These features are noncell-autonomous because T-ALL fromtail and thorax shares identical genomic abnormalities and functional disparities disappear in vivo and in prolonged in vitro assays. Importantly tail-derived T-ALL displays higher intrinsic resistance to cell-cycle-related drugs (ie, vincristine sulfate and cytarabine). Of note, T-ALL recovered from gonadal adipose tissues or from cocultures with adipocytes shares metabolic, cell-cycle, and phenotypic or chemoresistance features, with tail-derived T-ALL suggesting adipocytes may participate in the tail BM imprints on T-ALL. Altogether these results demonstrate that BM sites differentially orchestrate T-ALL propagation stamping specific features to leukemic cells such as quiescence and decreased response to cell-cycle-dependent chemotherapy.

Published
2017

28. Frontline Science: Exhaustion and senescence marker profiles on human T cells in BRGSF‐A2 humanized mice resemble those in human samples.

Author

Labarthe, Laura, Henriquez, Soledad, Lambotte, Olivier, Di Santo, James P., Grand, Roger, Pflumio, Françoise, Arcangeli, Marie‐Laure, Legrand, Nicolas, and Bourgeois, Christine

Subjects
HUMAN T cells, CORD blood, T cells, BLOOD cells
Abstract

This work sought to confirm the human‐like expression of exhaustion and senescence markers in a mouse model with a humanized immune system (HIS): the Balb/c Rag2KO IL2rgcKO SirpαNOD Flk2KO HLA‐A2HHD (BRGSF‐A2) mouse reconstituted with human CD34+ cord blood cells. With regard to senescence markers, the percentage of CD57+ T cells was higher in the bone marrow (BM) than in the spleen or blood. The same was true for KLRG1+ hCD8+ T cells. With regard to exhaustion markers, the percentage of programmed death 1 (PD‐1+) T cells was higher in the BM than in the spleen or blood; the same was true for TIGIT+ hCD4+ cells. These tissue‐specific differences were related to both higher proportions of memory T cells in BM and intrinsic differences in expression within the memory fraction. In blood samples from HIS mice and healthy human donors (HDs), we found that the percentage of KLRG1+ cells among hCD8+ T cells was lower in HIS compared to HDs. The opposite was true for CD4+ T cells. Unexpectedly, a high frequency of KLRG1+ cells was observed among naive T cells in HIS mice. CD57 expression on T cells was similar in blood samples from HIS mice and HDs. Likewise, PD‐1 expression was similar in the two systems, although a relatively low proportion of HIS hCD4+ T cells expressed TIGIT. The BRGSF‐A2 HIS mouse's exhaustion and senescence profile was tissue specific and relatively human like; hence, this mouse might be a valuable tool for determining the preclinical efficacy of immunotherapies. [ABSTRACT FROM AUTHOR]

Published
2020
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29. c-Myc is an important direct target of Notch1 in T-cell acute lymphoblastic leukemia/lymphoma

Author

Weng, Andrew P., Millholland, John M., Yashiro-Ohtani, Yumi, Arcangeli, Marie Laure, Lau, Arthur, Wai, Carol, Bianco, Cristina del, Rodriguez, Carlos G., Sai, Hong, Tobias, John, Li, Yeuming, Wolfe, Michael S., Shachaf, Cathy, Felsher, Dean, Blacklow, Stephen C., Pear, Warren S., and Aster, Jon C.

Subjects
Lymphocytic leukemia -- Diagnosis, T cells -- Research, Transduction -- Analysis, Biological sciences
Abstract

A preliminary test was conducted, where the effects of [gamma]-secretase blockade on c-myc mRNA levels was analyzed in five human T-cell lymphoblastic leukemias and lymphomas (T-ALL) cell lines, that require Notch signals for growth and was further encouraged with experiments, using c-myc-dependent murine T-ALL cells. The data showed that implicate c-myc is a developmentally regulated direct downstream target of Notch1, which contributes to the growth of T-ALL cells.

Published
2006

31. Control of developmentally primed erythroid genes by combinatorial co-repressor actions

Author

Stadhouders, Ralph, Cico, Alba, Stephen, Tharshana, Thongjuea, Supat, Kolovos, Petros, Baymaz, H. Irem, Yu, Xiao, Demmers, Jeroen, Bezstarosti, Karel, Maas, Alex, Barroca, Vilma, Kockx, Christel, Ozgur, Zeliha, van Ijcken, Wilfred, Arcangeli, Marie-Laure, Andrieu-Soler, Charlotte, Lenhard, Boris, Grosveld, Frank, Soler, Eric, Erasmus University Medical Center [Rotterdam] (Erasmus MC), Stabilité génétique, Cellules Souches et Radiations (SCSR (U_967)), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Computational Biology Unit [Bergen] (CBU), University of Bergen (UiB), Computational Regulatory Genomics, Imperial College London, Laboratoire d'Excellence : Biogenèse et pathologies du globule rouge (Labex Gr-Ex), Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Cell biology, Developmental Biology, Biochemistry, Molecular Genetics, Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Cellules Souches et Radiations (SCSR (U967 / UMR-E_008)), Université Paris-Sud - Paris 11 (UP11)-Université Paris Diderot - Paris 7 (UPD7)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Computational Biology Unit, Bergen Center for Computational Science, University of Bergen (UIB), Service Cellules Souches et Radiation (SCSR), and Université Paris-Saclay-Institut National de la Santé et de la Recherche Médicale (INSERM)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris Diderot - Paris 7 (UPD7)

Subjects
[SDV]Life Sciences [q-bio], Molecular Sequence Data, Article, SELECTIVELY MODULATES APOPTOSIS, Mice, ACUTE MEGAKARYOBLASTIC LEUKEMIA, Erythroid Cells, MD Multidisciplinary, Animals, Humans, Nuclear Receptor Co-Repressor 1, Erythropoiesis, Nuclear Receptor Co-Repressor 2, Amino Acid Sequence, Science & Technology, Base Sequence, Tumor Suppressor Proteins, BREAST-CANCER CELLS, CHIP-SEQ, Gene Expression Regulation, Developmental, Nuclear Proteins, LIM Domain Proteins, Multidisciplinary Sciences, GENOME, DNA-Binding Proteins, Repressor Proteins, DIFFERENTIATION, INTERFERON REGULATORY FACTOR-2, COMPLEXES FUNCTION, Science & Technology - Other Topics, Carrier Proteins, Transcription Factors
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 that together maintain an erythroid-specific gene expression programme primed for rapid activation until differentiation is induced. A combination of proteomics, functional genomics and in vivo studies presented here identifies known and novel co-repressors, most notably the ETO2 and IRF2BP2 proteins, involved in maintaining this primed state. The ETO2–IRF2BP2 axis, interacting with the NCOR1/SMRT co-repressor complex, suppresses the expression of the vast majority of archetypical erythroid genes and pathways until its decommissioning at the onset of terminal erythroid differentiation. Our experiments demonstrate that multimeric regulatory complexes feature a dynamic interplay between activating and repressing components that determines lineage-specific gene expression and cellular differentiation., Conserved sets of transcription factors (TFs) regulate hematopoiesis. Here, Stadhouders et al. show that IRF2BP2 is a component of the LDB1 TF complex and together with its co-repressor ETO2, enhances transcriptional repression, which plays a crucial role at the erythroid progenitor stage.

Published
2015
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32. Architectural and Functional Heterogeneity of Hematopoietic Stem/Progenitor Cells in Non-Del(5q) Myelodysplastic Syndromes

Author

Chesnais, Virginie, primary, Arcangeli, Marie-laure, additional, Delette, Caroline, additional, Rousseau, Alice, additional, Diop, M'boyba Khadija, additional, Lefevre, Andrea, additional, Cheok, Meyling H., additional, Chapuis, Nicolas, additional, Legros, Laurence, additional, Raynaud, Sophie, additional, Willems, Lise, additional, Bouscary, Didier, additional, Lauret, Evelyne, additional, Bernard, Olivier A., additional, Kosmider, Olivier, additional, Pflumio, Francoise, additional, and Fontenay, Michaela, additional

Published
2016
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34. Ptk7-Deficient Mice Have Decreased Hematopoietic Stem Cell Pools as a Result of Deregulated Proliferation and Migration

Author

Lhoumeau, Anne-Catherine, primary, Arcangeli, Marie-Laure, additional, De Grandis, Maria, additional, Giordano, Marilyn, additional, Orsoni, Jean-Christophe, additional, Lembo, Frédérique, additional, Bardin, Florence, additional, Marchetto, Sylvie, additional, Aurrand-Lions, Michel, additional, and Borg, Jean-Paul, additional

Published
2016
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37. The SCL/TAL1 Transcription Factor Represses the Stress Protein DDiT4/REDD1 in Human Hematopoietic Stem/Progenitor Cells

Author

Benyoucef, Aissa, primary, Calvo, Julien, additional, Renou, Laurent, additional, Arcangeli, Marie-Laure, additional, van den Heuvel, Anita, additional, Amsellem, Sophie, additional, Mehrpour, Maryam, additional, Larghero, Jerome, additional, Soler, Eric, additional, Naguibneva, Irina, additional, and Pflumio, Francoise, additional

Published
2015
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45. The SCL/TAL1 Transcription Factor Represses the Stress Protein DDi T4/ REDD1 in Human Hematopoietic Stem/Progenitor Cells.

Author

Benyoucef, Aissa, Calvo, Julien, Renou, Laurent, Arcangeli, Marie-Laure, Naguibneva, Irina, Pflumio, Francoise, Soler, Eric, van den Heuvel, Anita, Amsellem, Sophie, Mehrpour, Maryam, and Larghero, Jerome

Subjects
HEMATOPOIETIC stem cells, PROGENITOR cells, ADULT T-cell leukemia, PHYSIOLOGY
Abstract

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 not clarified. In this study, we show that knockdown (KD) or short-term conditional over-expression (OE) of TAL1 in human HSPC ex vivo, respectively, blocks and maintains hematopoietic potentials, affecting proliferation of human HSPC. Comparative gene expression analyses of TAL1/KD and TAL1/OE human HSPC revealed modifications of cell cycle regulators as well as previously described TAL1 target genes. Interestingly an inverse correlation between TAL1 and DNA damage-induced transcript 4 (DDiT4/REDD1), an inhibitor of the mammalian target of rapamycin (mTOR) pathway, is uncovered. Low phosphorylation levels of mTOR target proteins in TAL1/KD HSPC confirmed an interplay between mTOR pathway and TAL1 in correlation with TAL1-mediated effects of HSPC proliferation. Finally chromatin immunoprecipitation experiments performed in human HSPC showed that DDiT4 is a direct TAL1 target gene. Functional analyses showed that TAL1 represses DDiT4 expression in HSPCs. These results pinpoint DDiT4/REDD1 as a novel target gene regulated by TAL1 in human HSPC and establish for the first time a link between TAL1 and the mTOR pathway in human early hematopoietic cells. S tem C ells 2015;33:2268-2279 [ABSTRACT FROM AUTHOR]

Published
2015
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49. The thymus exports long-lived fully committed T cell precursors that can colonize primary lymphoid organs.

Author

Lambolez, Florence, Arcangeli, Marie-Laure, Joret, Anne-Marie, Pasqualetto, Valérie, Cordier, Corinne, di Santo, James P., Rocha, Benedita, and Ezine, Sophie

Subjects
*T cell receptors, *THYMUS, *LYMPHOID tissue, *BINDING sites, *CELL membranes, *LEUCOCYTES
Abstract

Thymic export of cells is believed to be restricted to mature T cells. Here we show that the thymus also exports fully committed T cell precursors that colonize primary lymphoid organs. These precursor cells exited the thymus before T cell receptor rearrangements and colonized lymphoid organs such as the thymus and the gut. Migration of the thymic T cell–committed precursors led to permanent colonization of the gut precursor compartment, improved the capacity of gut precursors to further differentiate into T cells and was sufficient for the generation of 'euthymic like' CD8αα+ intraepithelial lymphocytes. These data demonstrate a new function for the thymus in peripheral seeding with T cell precursors that become long lived after thymus export. [ABSTRACT FROM AUTHOR]

Published
2006
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50. Ontogenic Changes in Hematopoietic Hierarchy Determine Pediatric Specificity and Disease Phenotype in Fusion Oncogene-Driven Myeloid Leukemia

Author

Lopez, Cécile K, Noguera, Esteve, Stavropoulou, Vaia, Robert, Elie, Aid, Zakia, Ballerini, Paola, Bilhou-Nabera, Chrystèle, Lapillonne, Hélène, Boudia, Fabien, Thirant, Cécile, Fagnan, Alexandre, Arcangeli, Marie-Laure, Kinston, Sarah J, Diop, M'Boyba, Job, Bastien, Lecluse, Yann, Brunet, Erika, Babin, Loélia, Villeval, Jean Luc, Delabesse, Eric, Peters, Antoine HFM, Vainchenker, William, Gaudry, Muriel, Masetti, Riccardo, Locatelli, Franco, Malinge, Sébastien, Nerlov, Claus, Droin, Nathalie, Lobry, Camille, Godin, Isabelle, Bernard, Olivier A, Göttgens, Berthold, Petit, Arnaud, Pflumio, Françoise, Schwaller, Juerg, and Mercher, Thomas

Subjects
Adolescent, Oncogene Proteins, Fusion, Age Factors, Infant, 3. Good health, Leukemia, Myeloid, Acute, Mice, Child, Preschool, Tumor Cells, Cultured, Animals, Humans, Female, Child, Neoplasm Transplantation, Transcription Factors
Abstract

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, are associated with acute megakaryoblastic or other myeloid leukemia subtypes in an age-dependent manner. Analysis of a novel inducible transgenic mouse model showed that ETO2-GLIS2 expression in fetal hematopoietic stem cells induced rapid megakaryoblastic leukemia whereas expression in adult bone marrow hematopoietic stem cells resulted in a shift toward myeloid transformation with a strikingly delayed in vivo leukemogenic potential. Chromatin accessibility and single-cell transcriptome analyses indicate ontogeny-dependent intrinsic and ETO2-GLIS2-induced differences in the activities of key transcription factors, including ERG, SPI1, GATA1, and CEBPA. Importantly, switching off the fusion oncogene restored terminal differentiation of the leukemic blasts. Together, these data show that aggressiveness and phenotypes in pediatric acute myeloid leukemia result from an ontogeny-related differential susceptibility to transformation by fusion oncogenes. SIGNIFICANCE: This work demonstrates that the clinical phenotype of pediatric acute myeloid leukemia is determined by ontogeny-dependent susceptibility for transformation by oncogenic fusion genes. The phenotype is maintained by potentially reversible alteration of key transcription factors, indicating that targeting of the fusions may overcome the differentiation blockage and revert the leukemic state.See related commentary by Cruz Hernandez and Vyas, p. 1653.This article is highlighted in the In This Issue feature, p. 1631.

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