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Regulation of Lozenge Transcription Factor Activity and Blood Cell Development by MLF and Its Partner Dnaj-1 Aichun Chen

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Regulation of Lozenge Transcription Factor Activity and Blood Cell Development by MLF and Its Partner Dnaj-1 Aichun Chen Regulation of lozenge transcription factor activity and blood cell development by MLF and its partner DnaJ-1 Aichun Chen To cite this version: Aichun Chen. Regulation of lozenge transcription factor activity and blood cell development by MLF and its partner DnaJ-1. Development Biology. Université Paul Sabatier - Toulouse III, 2017. English. NNT : 2017TOU30064. tel-01816933 HAL Id: tel-01816933 https://tel.archives-ouvertes.fr/tel-01816933 Submitted on 15 Jun 2018 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. 5)µ4& &OWVFEFMPCUFOUJPOEV %0$503"5%&-6/*7&34*5²%&506-064& %ÏMJWSÏQBS Université Toulouse 3 Paul Sabatier (UT3 Paul Sabatier) 1SÏTFOUÏFFUTPVUFOVFQBS Aichun CHEN le 27 Juin 2017 5JUSF Regulation of Lozenge transcription factor activity and blood cell development by MLF and its partner DnaJ-1 ²DPMFEPDUPSBMF et discipline ou spécialité ED BSB : Biologie du développement 6OJUÏEFSFDIFSDIF Centre de Biologie du Développement, CNRS UMR 5547 %JSFDUFVSUSJDF T EFʾÒTF Dr. Lucas WALTZER Dr. Marc HAENLIN Jury: Pr. Christiane BIERKAMP, président Dr. Bruno LEMAITRE, rapporteur Dr. Marie-Bérengere TROADEC, rapportrice Dr. Magalie LECOURTOIS, rapportrice Dr. Anne PLESSIS, examinatrice Dr. Lucas WALTZER, directeur de thèse Dr. Marc HAENLIN, directeur de thèse 1 Acknowledgements Taking advantage of this opportunity that gives me this manuscript, I would like to express my sincere and special gratitude to everyone who has helped me during my four years of PhD study in Toulouse, France. Firstly, I would like to express my special appreciations and thanks to my supervisor, Dr. Lucas Waltzer, who has been a tremendous mentor for me. Thank you for adopting me into CBD family and for continuous patience and support on both my research and my life in France. Your guidance helped me a lot all the time in research work and this thesis writing. Besides my supervisor, I would like to thank my co-supervisor, Dr. Marc Haenlin, for his support and enthusiasm and the rest of my thesis committee members, Prof. Christiane Bierkamp, Dr. Bruno Lemaitre, Dr. Marie-Bérengere Troadec, Dr. Magalie Lecourtois and Dr. Anne Plessis for their insightful comments and encouragement, but also for making my defense be an enjoyable moment and hard questions which incented me to widen my research horizon. My sincere thanks also go to Dr. Vanessa Gobert, Dr. Fernando Roch, Dr. Billel Benmimoun, Dr. Marion Miller and our technician Benoir Augé and Sandra Bernat-Fabre, those who taught me how to perform experiments, how to analyze experimental data, how to use various scientific instruments as well as always answer my questions kindly and patiently. I also would like to thank my two Chinese colleagues, Dr. Qiongyue Xu and Lu Wei, at the lab, who helped me a lot when I had a hard time and made me feel like at home when I felt lonely. Last but not the least, I would like to thank my family. Any words cannot express how grateful I am to my mother and my father, for all of the sacrifices that they have made on my behalf and for supporting me spiritually all the time. i ii Contents Acknowledgements ................................................................................................................. i Abstract .................................................................................................................................. v Résumé ................................................................................................................................. vii Foreword ............................................................................................................................. ixx List of abbreviations ............................................................................................................ xii List of figures ....................................................................................................................... xv List of tables ....................................................................................................................... xvii Chapter I Introduction ....................................................................................................... 1 1. A general description of hematopoiesis and leukemia ................................................................ 3 1.1. Hematopoiesis in mammals .................................................................................................................... 3 1.1.1. Ontogeny of the mammalian hematopoiesis ...................................................................................................... 3 1.1.2. Functions of mature blood cells .......................................................................................................................... 7 1.1.3. Genetic control of the mammalian hematopoietic system ............................................................................... 8 1.1.3.1 The hematopoietic niches ................................................................................................................................ 8 1.1.3.2 Lineages specific transcription factors and signaling pathways controlling blood cell differentiation . 10 1.2. Leukemia in human ............................................................................................................................... 11 1.2.1. Classification of leukemia ................................................................................................................................. 11 1.2.2. Acute myeloid leukemia .................................................................................................................................... 12 1.2.2.1. Classification of acute myeloid leukemia .................................................................................................... 12 1.2.2.2. Pathophysiology of acute myeloid leukemia ............................................................................................... 13 1.2.2.3. Current therapy of acute myeloid leukemia .............................................................................................. 14 2. Drosophila: a simplified model to study the mammalian hematopoiesis ................................ 15 2.1. Ontogeny of Drosophila hematopoietic system ................................................................................... 16 2.1.1. Embryonic hematopoiesis ................................................................................................................................. 17 2.1.2. Larval hematopoiesis ......................................................................................................................................... 18 2.1.3. Hematopoiesis in adult Drosophila ................................................................................................................... 19 2.2. Functions of Drosophila hemocytes ...................................................................................................... 20 2.2.1. Prohemacytes ..................................................................................................................................................... 20 2.2.2. Plasmatocytes ..................................................................................................................................................... 21 2.2.3. Crystal cells ........................................................................................................................................................ 22 2.2.4. Lamellocytes ....................................................................................................................................................... 22 2.3. Genetic control of Drosophila hematopoiesis ...................................................................................... 23 2.3.1 PSC in Drosophila hematopoiesis ...................................................................................................................... 23 2.3.2 ROS in Drosophila hematopoiesis ..................................................................................................................... 23 2.3.3. Genetic control of blood cell fate ...................................................................................................................... 24 3. RUNX family of transcription factors in hematopoiesis and leukemia .................................. 27 3.1. The Core-binding factors family .......................................................................................................... 27 3.2. Identification of RUNX1 in mammals ................................................................................................. 28 3.2.1. Structure and isoforms of RUNX1 transcription factor ................................................................................ 29 3.2.2. RUNX1: a master transcriptional regulator of hematopoietic development ............................................... 31 3.2.3. Post-translational modifications of RUNX1 ...................................................................................................
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