Functions of the transcription factor Lyl-1 in the hematopoietic development of the embryo : Focus on yolk sac macrophages and hematopoietic stem cells

Abstract : During ontogeny, hematopoietic progenitors are generated in three independent waves, the first two (primitive and transient definitive) develop from the yolk sac (YS), before the appearance of Hematopoietic Stem Cells (HSC) that occurs later in the Aorta‐Gonad‐Mesonephros (AGM), in the third and definitive wave. Both Tal1/SCL and its paralog Lyl‐1 belong to the transcriptional complex that regulates hematopoietic progenitor development. While Tal‐1/SCL is mandatory for the specification of hematopoietic progenitors from the three embryonic waves, to date the functions of Lyl‐1 during developmental hematopoiesis remains largely unknown. By making use of the lacZ reporter from the Lyl‐1lacZ mice, we previously found that Lyl‐1 marks and regulates YS macrophage progenitors from the primitive wave (MΦPrim), and embryonic microglia. In a RNA‐seq analysis, we show that MΦPrim gene expression landscape is clearly distinct from later transient definitive MΦ progenitors, reflecting their primitive status. Lyl‐1 invalidation also influences some inflammatory signalling pathways and also leads to the abnormal activation of microglia genes involved in synaptic regulation. In the definitive wave, we found that Lyl‐1 disruption leads to a reduced efficiency of long‐term reconstitution by HSC from embryonic day (E)10 AGM and reduced HSC pool size in E12 and E14 fetal liver. The reduction of the HSC pool results from a higher apoptosis level in Lyl‐1LacZ/LacZ HSCs restricted to the AGM stage. Together, our data establish that Lyl‐1 regulates the development of MΦPrim progenitors and HSC pool size soon after they are generated.
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Deshan Ren. Functions of the transcription factor Lyl-1 in the hematopoietic development of the embryo : Focus on yolk sac macrophages and hematopoietic stem cells. Embryology and Organogenesis. Université Paris-Saclay, 2019. English. ⟨NNT : 2019SACLS189⟩. ⟨tel-02186350⟩

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