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Molecular control of the Endothelial to Hematopoietic Transition

Abstract : Hematopoietic Stem Cells (HSCs) are the basis of the regulated functioning of the hematopoietic system throughout the life of the individual. In adult amniotes, HSCs reside in the bone marrow but are produced very early during development, transiently and in small numbers, at the level the dorsal aorta from specialized Endothelial Cells (EC), termed Hemogenic Endothelial Cell (HEC), themselves derived from non-hemogenic ECs. HECs, under the influence of signals yet to be defined, lose their endothelial fate and acquire a hematopoietic identity through a mechanism designated as Endothelial-To-Hematopoietic transition (EHT). How HECs are specified and how EHT is fine-tuned remain unanswered questions but has major implication in regenerative medicine. We recently designed an ex vivo culture system, starting from the quail pre-somitic mesoderm, that mimics the steps occurring in the aorta to produce the first HSCs. We have exploited this system to isolate specific transcriptomic signatures for the passage from the mesoderm to ECs, from ECs to HECs and from HECs to HSCs. Using an ensemble of systems biology approaches; we have isolated specific molecular signatures for one or the other cell states and have emphasized on the identification of genes implicated in the specification of the hemogenic endothelium and the control of EHT. Two key signaling pathways (Wnt and Notch) and a specific gene (POFUT2) has been shown to play a crucial role in the EHT. Taken together our results should help to better define key steps in the commitment towards HSC to further produce safe and robust cells for therapeutic purposes.
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  • HAL Id : tel-02950852, version 1

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Hanane Khoury. Molecular control of the Endothelial to Hematopoietic Transition. Cellular Biology. Sorbonne Université, 2019. English. ⟨NNT : 2019SORUS166⟩. ⟨tel-02950852⟩

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