1. Novel pathway for megakaryocyte production after in vivo conditional eradication of integrin αIIb-expressing cells
- Author
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Thierry Kortulewski, Pierre Vaigot, Pascal Soularue, Olivier Alibert, Alexandre Pawlik, Diana Tronik-Le Roux, Beatrice Jacquelin, Xavier Gidrol, Christophe Joubert, Gaëtan Gruel, Laboratoire de Cancérologie Expérimentale (LCE), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Service de Génomique Fonctionnelle, Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Supported by funds from the Commissariat à l'Energie Atomique (CEA) and the Association Française contre les Myopathies (AFM) and by a postdoctoral training grant from Genopole-Evry., and We thank Drs A. Galy and E. Lauret for their assistance in cell culture studies, J.-M. Egly and Y. Senis for critical reading of the manuscript, and Dr G. Marguerie, who initially established the CEA microarray platform. We also thank the staff of the Genethon mouse facility and P. Flament and V. Neuville for outstanding work in animal care at the CEA-FAR mouse facility. All the animal studies reported were performed in accordance with current French regulations (Décret no. 87-848 modifié, Ministère de l'Agriculture).
- Subjects
Myeloid ,Cellular differentiation ,Biochemistry ,Mice ,0302 clinical medicine ,Megakaryocyte ,Myeloid Cells ,MESH: Animals ,MESH: Proteins ,Lymphocytes ,MESH: Platelet Membrane Glycoprotein IIb* / genetics ,0303 health sciences ,education.field_of_study ,MESH: Bone Marrow Cells / physiology ,Polycomb Repressive Complex 2 ,MESH: Regeneration ,Hematology ,3. Good health ,Cell biology ,DNA-Binding Proteins ,Haematopoiesis ,medicine.anatomical_structure ,Myelopoiesis ,Megakaryocytes ,MESH: Polycomb Repressive Complex 2 ,Platelet Membrane Glycoprotein IIb ,MESH: DNA Nucleotidylexotransferase / genetics ,MESH: Mice, Transgenic ,Immunology ,Population ,Bone Marrow Cells ,Mice, Transgenic ,MESH: Lymphocytes / physiology ,Biology ,MESH: Hematopoiesis ,03 medical and health sciences ,MESH: Gene Expression Profiling ,DNA Nucleotidylexotransferase ,[SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN] ,MESH: Megakaryocytes / cytology ,medicine ,MESH: Enhancer of Zeste Homolog 2 Protein ,[SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO] ,Animals ,Regeneration ,Cell Lineage ,Enhancer of Zeste Homolog 2 Protein ,Lymphopoiesis ,education ,MESH: Mice ,MESH: Myeloid Cells / physiology ,030304 developmental biology ,MESH: DNA-Binding Proteins / genetics ,Gene Expression Profiling ,MESH: Histone-Lysine N-Methyltransferase ,Proteins ,Histone-Lysine N-Methyltransferase ,Cell Biology ,MESH: Cell Lineage ,Molecular biology ,Hematopoiesis ,Gene expression profiling ,030215 immunology - Abstract
Our knowledge of the molecular mechanisms that regulate hematopoiesis in physiologic and pathologic conditions is limited. Using a molecular approach based on cDNA microarrays, we demonstrated the emergence of an alternative pathway for mature bone marrow cell recovery after the programmed and reversible eradication of CD41+ cells in transgenic mice expressing a conditional toxigene targeted by the platelet αIIb promoter. The expression profile of the newly produced CD41+ cells showed high levels of transcripts encoding Ezh2, TdT, Rag2, and various immunoglobulin (Ig) heavy chains. In this context, we identified and characterized a novel population of Lin-Sca-1hic-Kit- cells, with a lymphoid-like expression pattern, potentially involved in the reconstitution process. Our study revealed novel transcriptional cross talk between myeloid and lymphoid lineages and identified gene expression modifications that occur in vivo under these particular stress conditions, opening important prospects for therapeutic applications.
- Published
- 2005
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