Novel pathway for megakaryocyte production after in vivo conditional eradication of integrin alphaIIb-expressing cells.
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 alphaIIb 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-1hi c-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.
Jacquelin
Beatrice
B
Laboratoire de Génomique et Radiobiologie de l'Hématopoïèse, Service de Génomique Fonctionnelle, Commissariat à l'Energie Atomique, Evry, France.
Kortulewski
Thierry
T
Vaigot
Pierre
P
Pawlik
Alexandre
A
Gruel
Gaetan
G
Alibert
Olivier
O
Soularue
Pascal
P
Joubert
Christophe
C
Gidrol
Xavier
X
Tronik-Le Roux
Diana
D
D000818:Animals; D001854:Bone Marrow Cells / Q000502:physiology*; D019070:Cell Lineage; D004253:DNA Nucleotidylexotransferase / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D000071221:Enhancer of Zeste Homolog 2 Protein; D020869:Gene Expression Profiling; D006410:Hematopoiesis; D011495:Histone-Lysine N-Methyltransferase; D008214:Lymphocytes / Q000502:physiology; D008533:Megakaryocytes / Q000166:cytology*; D051379:Mice; D008822:Mice, Transgenic; D022423:Myeloid Cells / Q000502:physiology; D040201:Platelet Membrane Glycoprotein IIb / Q000235:genetics; D063151:Polycomb Repressive Complex 2; D011506:Proteins; D012038:Regeneration
D004268:DNA-Binding Proteins; D040201:Platelet Membrane Glycoprotein IIb; D011506:Proteins; C499308:Rag2 protein, mouse; C064655:V(D)J recombination activating protein 2; D000071221:Enhancer of Zeste Homolog 2 Protein; C498410:Ezh2 protein, mouse; D011495:Histone-Lysine N-Methyltransferase; D063151:Polycomb Repressive Complex 2; D004253:DNA Nucleotidylexotransferase