Team 14: Epigenetic regulation and hematopoiesis

Research

Our projects aim at deciphering the mechanisms that regulate gene expression during bood cell development and how these regulatory mechanisms go awry in patholocial situations.

Haematopoiesis involves commitment, proliferation and differentiation of hematopoietic stem cells into several specialised blood cell types that play conspicuous roles in maintaining the homeostasis of the organism, notably by participating in the immune response and in removing dead or cancerous cells. Yet, these cells have both protective and deleterious functions in antimicrobial defence, auto-immune diseases, inflammatory reactions, metabolic disorders or tumorigenesis. Moreover, mutations affecting blood cell development can lead to various deadly haemopathies, including leukemia. Hence, deciphering how the fate and function of these cells is controlled is a field of intense investigation with strong physio-pathological implications.

Our general objective is to characterise the gene networks that control blood cell development in normal or pathological situations (infection, cancer...). To do so we use a combination of genetic, molecular, cellular and developemental approaches using mostly Drosophila melanogaster as a model organism. Indeed work from several groups including ours revealed striking similiarities between mammalian and Drosophila hematopoietic systems at the functional, ontogenic and molecular levels.

In particular, we seek to unravel the molecular characteristic of the Drosophila blood cell progenitor populations and to decipher the mechanisms of action and of regulation of conserved transcription factors and epigenetic enzymes whose human homologs are implicated in leukemia.

Our projects not only deals with the transcriptional regulation of genome expression but also cover post-transcriptional regulatory processes at the epitranscriptomic and post-translational levels.

Given the phylogenetic conervation of the gene netwroks regulating hematopoiesis and of the underlying molecular mechanisms, our work in Drosophila has a direct impact on the understanding of the fundamental processes controlling the development and the homeostasis of the hematopoietic system in Human, with implications in term of human heatlh.

Our long-term goal is to use cellular models and model organisms to understand the molecular processes that underlie human blood cell diseases.

Research thematics

People

Last Name First Name Position Contact
Nadege ANGLARET profile picture ANGLARET Nadege Technical Assistant
Romane BERTRAND profile picture BERTRAND Romane Assistant Engineer
Vincent GERDY profile picture GERDY Vincent Ph.D Student
Guerric GILBERT profile picture GILBERT Guerric Ph.D Student
Yoan RENAUD profile picture RENAUD Yoan Research Engineer
Camille TESTE profile picture TESTE Camille Ph.D Student
Laurence VANDEL profile picture VANDEL Laurence Senior Research Fellow
Lucas WALTZER profile picture WALTZER Lucas Principal Investigator

Publications

  • 2022
    • M. Bortolin-Cavaille, Q. Aurelie, T. Supuni, J. Thomas, A. Sas-Chen, S. Sharma, C. Plisson-Chastang, L. Vandel, P. Blader, D. Lafontaine, S. Schwartz, J. Meier and J. Cavaille, “Probing small ribosomal subunit RNA helix 45 acetylation across eukaryotic evolution.”, Nucleic Acids Res., 2022.
  • 2021
    • S. Lamoine, M. Cumenal, D. Barriere, V. Pereira, M. Fereyrolles, L. Prival, J. Barbier, L. Boudieu, E. Brasset, B. Bertin, Y. Renaud, E. Miot-Noirault, M. Civiale, D. Balayssac, Y. Aissouni, A. Eschalier and J. Busserolles, “The Class I HDAC Inhibitor, MS-275, Prevents Oxaliplatin-Induced Chronic Neuropathy and Potentiates Its Antiproliferative Activity in Mice.”, International journal of molecular sciences, vol. 23 (1) , 2021.
    • A. Quillien, G. Gilbert, M. Boulet, S. Ethuin, L. Waltzer and L. Vandel, “Prmt5 promotes vascular morphogenesis independently of its methyltransferase activity.”, PLoS Genet., vol. 17 (6) , pp. e1009641, 2021.
    • D. Rodrigues, Y. Renaud, K. VijayRaghavan, L. Waltzer and M. Inamdar, “Differential activation of JAK-STAT signaling reveals functional compartmentalization in Drosophila blood progenitors.”, eLife, vol. 10 , 2021.
    • J. Francis, J. Gardiner, Y. Renaud, R. Chauhan, Y. Weinstein, C. Gomez-Sanchez, A. Lefrancois-Martinez, J. Bertherat, P. Val and A. Swain, “HOX genes promote cell proliferation and are potential therapeutic targets in adrenocortical tumours.”, British journal of cancer, vol. 124 (4) , pp. 805–816, 2021.
    • M. Boulet, Y. Renaud, F. Lapraz, B. Benmimoun, L. Vandel and L. Waltzer, “Characterization of the Drosophila Adult Hematopoietic System Reveals a Rare Cell Population With Differentiation and Proliferation Potential.”, Frontiers in cell and developmental biology, vol. 9 , pp. 739357, 2021.
    • A. Kumar, Y. Kasikci, A. Badredine, K. Azzag, M. Quintyn Ranty, F. Zaidi, N. Aragou, C. Mazerolles, B. Malavaud, M. Mendoza-Parra, L. Vandel and H. Gronemeyer, “Patient-matched analysis identifies deregulated networks in prostate cancer to guide personalized therapeutic intervention.”, Am J Cancer Res, vol. 11 (11) , pp. 5299–5318, 2021.
  • 2020
    • J. Francis, J. Gardiner, Y. Renaud, R. Chauhan, Y. Weinstein, C. Gomez-Sanchez, A. Lefrancois-Martinez, J. Bertherat, P. Val and A. Swain, “HOX genes promote cell proliferation and are potential therapeutic targets in adrenocortical tumours.”, British journal of cancer, 2020.
    • J. Lepesant, C. Iampietro, E. Galeota, B. Auge, M. Aguirrenbengoa, C. Merce, C. Chaubet, V. Rocher, M. Haenlin, L. Waltzer, M. Pelizzola and L. Di Stefano, “A dual role of dLsd1 in oogenesis: regulating developmental genes and repressing transposons.”, Nucleic Acids Res., vol. 48 (3) , pp. 1206–1224, 2020.
  • 2019
    • C. Immarigeon, S. Bernat-Fabre, B. Auge, C. Faucher, V. Gobert, M. Haenlin, L. Waltzer, A. Payet, D. Cribbs, H. Bourbon and M. Boube, “Drosophila Mediator Subunit Med1 Is Required for GATA-Dependent Developmental Processes: Divergent Binding Interfaces for Conserved Coactivator Functions.”, Molecular and cellular biology, vol. 39 (7) , 2019.
  • 2018
    • L. Fauquier, K. Azzag, M. Parra, A. Quillien, M. Boulet, S. Diouf, G. Carnac, L. Waltzer, H. Gronemeyer and L. Vandel, “CBP and P300 regulate distinct gene networks required for human primary myoblast differentiation and muscle integrity.”, Scientific reports, vol. 8 (1) , pp. 12629, 2018.
    • M. Boulet, M. Miller, L. Vandel and L. Waltzer, “From Drosophila Blood Cells to Human Leukemia.”, Advances in experimental medicine and biology, vol. 1076 , pp. 195–214, 2018.
  • 2017
    • F. Bajanca and L. Vandel, “Epigenetic Regulators Modulate Muscle Damage in Duchenne Muscular Dystrophy Model.”, PLoS currents, vol. 9 , 2017.
    • M. Miller, A. Chen, V. Gobert, B. Auge, M. Beau, O. Burlet-Schiltz, M. Haenlin and L. Waltzer, “Control of RUNX-induced repression of Notch signaling by MLF and its partner DnaJ-1 during Drosophila hematopoiesis.”, PLoS Genet., vol. 13 (7) , pp. e1006932, 2017.
  • 2016
    • M. Letourneau, F. Lapraz, A. Sharma, N. Vanzo, L. Waltzer and M. Crozatier, “Drosophila hematopoiesis under normal conditions and in response to immune stress.”, FEBS Lett., vol. 590 (22) , pp. 4034–4051, 2016.
  • 2015
    • B. Benmimoun, C. Polesello, M. Haenlin and L. Waltzer, “The EBF transcription factor Collier directly promotes Drosophila blood cell progenitor maintenance independently of the niche.”, Proc. Natl. Acad. Sci. U.S.A., vol. 112 (29) , pp. 9052–7, 2015.
    • J. Batut, C. Duboe and L. Vandel, “Expression patterns of CREB binding protein (CREBBP) and its methylated species during zebrafish development.”, The International journal of developmental biology, vol. 59 (4-6) , pp. 229–34, 2015.
    • B. Benmimoun, M. Haenlin and L. Waltzer, “Haematopoietic progenitor maintenance by EBF/Collier: beyond the Niche.”, Cell cycle (Georgetown, Tex.), vol. 14 (22) , pp. 3517–8, 2015.
    • B. Benmimoun, M. Haenlin and L. Waltzer, “Blood cell progenitor maintenance: Collier barks out of the niche.”, Fly (Austin), vol. 9 (4) , pp. 160–4, 2015.
  • 2014
    • O. Breig, S. Bras, N. Martinez Soria, D. Osman, O. Heidenreich, M. Haenlin and L. Waltzer, “Pontin is a critical regulator for AML1-ETO-induced leukemia.”, Leukemia, vol. 28 (6) , pp. 1271–9, 2014.
  • 2012
    • V. Gobert, M. Haenlin and L. Waltzer, “Myeloid leukemia factor: a return ticket from human leukemia to fly hematopoiesis.”, Transcription, vol. 3 (5) , pp. 250–4, 2012.
    • B. Benmimoun, C. Polesello, L. Waltzer and M. Haenlin, “Dual role for Insulin/TOR signaling in the control of hematopoietic progenitor maintenance in Drosophila.”, Development, vol. 139 (10) , pp. 1713–7, 2012.
    • S. Bras, S. Martin-Lanneree, V. Gobert, B. Auge, O. Breig, M. Sanial, M. Yamaguchi, M. Haenlin, A. Plessis and L. Waltzer, “Myeloid leukemia factor is a conserved regulator of RUNX transcription factor activity involved in hematopoiesis.”, Proc. Natl. Acad. Sci. U.S.A., vol. 109 (13) , pp. 4986–91, 2012.
  • 2011
    • D. Ceschin, M. Walia, S. Wenk, C. Duboe, C. Gaudon, Y. Xiao, L. Fauquier, M. Sankar, L. Vandel and H. Gronemeyer, “Methylation specifies distinct estrogen-induced binding site repertoires of CBP to chromatin.”, Genes Dev., vol. 25 (11) , pp. 1132–46, 2011.
    • A. Hijazi, M. Haenlin, L. Waltzer and F. Roch, “The Ly6 protein coiled is required for septate junction and blood brain barrier organisation in Drosophila.”, PLoS ONE, vol. 6 (3) , pp. e17763, 2011.
    • C. Polesello, F. Roch, V. Gobert, M. Haenlin and L. Waltzer, “Modeling cancers in Drosophila.”, Progress in molecular biology and translational science, vol. 100 , pp. 51–82, 2011.
    • J. Batut, C. Duboe and L. Vandel, “The methyltransferases PRMT4/CARM1 and PRMT5 control differentially myogenesis in zebrafish.”, PLoS ONE, vol. 6 (10) , pp. e25427, 2011.
  • 2010
    • V. Gobert, D. Osman, S. Bras, B. Auge, M. Boube, H. Bourbon, T. Horn, M. Boutros, M. Haenlin and L. Waltzer, “A genome-wide RNA interference screen identifies a differential role of the mediator CDK8 module subunits for GATA/ RUNX-activated transcription in Drosophila.”, Molecular and cellular biology, vol. 30 (11) , pp. 2837–48, 2010.
    • A. Avet-Rochex, K. Boyer, C. Polesello, V. Gobert, D. Osman, F. Roch, B. Auge, J. Zanet, M. Haenlin and L. Waltzer, “An in vivo RNA interference screen identifies gene networks controlling Drosophila melanogaster blood cell homeostasis.”, BMC Dev. Biol., vol. 10 , pp. 65, 2010.
    • D. Osman, V. Gobert, M. Haenlin and L. Waltzer, “[Drosophila as a new model system for leukaemia].”, Med Sci (Paris), vol. 26 (1) , pp. 9–11, 2010.
    • I. Fernandes, H. Chanut-Delalande, P. Ferrer, Y. Latapie, L. Waltzer, M. Affolter, F. Payre and S. Plaza, “Zona pellucida domain proteins remodel the apical compartment for localized cell shape changes.”, Dev. Cell, vol. 18 (1) , pp. 64–76, 2010.
  • 2009
    • A. Hijazi, W. Masson, B. Auge, L. Waltzer, M. Haenlin and F. Roch, “boudin is required for septate junction organisation in Drosophila and codes for a diffusible protein of the Ly6 superfamily.”, Development, vol. 136 (13) , pp. 2199–209, 2009.
    • D. Osman, V. Gobert, F. Ponthan, O. Heidenreich, M. Haenlin and L. Waltzer, “A Drosophila model identifies calpains as modulators of the human leukemogenic fusion protein AML1-ETO.”, Proc. Natl. Acad. Sci. U.S.A., vol. 106 (29) , pp. 12043–8, 2009.