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Role of the environment in establishment of definitive haematopoiesis

Abstract : Haematopoiesis is the process of haematopoietic stem cell (HSC) generation conserved in all vertebrates. During the embryonic development, two successive waves of haematopoiesis occur – the primitive and the definitive wave. The first one gives rise to erythrocytes, macrophages and neutrophils. During the second one, HSCs emerge from the ventral wall of dorsal aorta (DA) in the aorta-gonads-mesonephros (AGM) region by a process called endothelial-to-haematopoietic transition or EHT.In the last years, several studies performed in mammals have shown that the microenvironment plays a key role in haematopoiesis. During my thesis I have studied the role of the microenvironment in definitive haematopoiesis in the zebrafish embryo. I have described several cell components present in the AGM and evaluated their contribution to the haematopoiesis. I further analysed two of those players: macrophages and sympathetic nervous system. Each of them plays a specific role during the definitive wave of haematopoiesis. Macrophages mobilise nascent HSCs from the AGM to allow their intravasation and colonisation of haematopoietic organs. Catecholamines synthetized by sympathetic nervous system control EHT through the activation of beta2b and beta3 receptors in the AGM.In conclusion, we have shown that the microenvironment can substantially influence the definitive haematopoiesis in the zebrafish by distinct mechanisms. These findings would help to understand the mechanism of HSC generation and potentially to allow in vitro HSC production.
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Jana Trávníčková. Role of the environment in establishment of definitive haematopoiesis. Hematology. Université Montpellier, 2016. English. ⟨NNT : 2016MONT3510⟩. ⟨tel-02937606⟩

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