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 Blood, 15 September 2005, Vol. 106, No. 6, pp. 1965-1974.
Prepublished online as a Blood First Edition Paper on June 9, 2005; DOI 10.1182/blood-2004-10-3975.

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HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY

Novel pathway for megakaryocyte production after in vivo conditional eradication of integrin {alpha}IIb-expressing cells

Beatrice Jacquelin, Thierry Kortulewski, Pierre Vaigot, Alexandre Pawlik, Gaetan Gruel, Olivier Alibert, Pascal Soularue, Christophe Joubert, Xavier Gidrol, and Diana Tronik-Le Roux

From the Laboratoire de Génomique et Radiobiologie de l'Hématopoïèse and Laboratoire d'Exploration Fonctionnelle des Génomes, Service de Génomique Fonctionnelle, Commissariat à l'Energie Atomique, Evry, France; and the Laboratoire de Cancérologie Expérimentale, Fontenay-aux-Roses, France.

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 {alpha}IIb 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.


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