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Pré-Publication, Document De Travail Année : 2020

Lyl-1 marks and regulates primitive macrophages and microglia development

Shoutang Wang
  • Fonction : Auteur
Deshan Ren
  • Fonction : Auteur
Anna-Lila Kaushik
  • Fonction : Auteur
Gabriel Matherat
  • Fonction : Auteur
Yann Lécluse
  • Fonction : Auteur
Dominik Filipp
  • Fonction : Auteur
Hana Raslova

Résumé

During ontogeny, resident macrophages (MΦs) of the nervous system emerge from haematopoietic stem cell-independent progenitors originating in the Yolk Sac (YS), so that factors impairing YS MΦ development may lead to neurodevelopmental disorders resulting from defective brain resident MΦ.
Here we show that Lyl-1, a bHLH transcription factor related to Scl/Tal-1, marks primitive macrophage (MΦ Prim ) progenitors in the YS. Transcriptomic analysis of YS MΦ progenitors indicated that MΦ Prim progenitors present at embryonic day (E) 9 are clearly distinct from those present at E10. Lyl-1 bHLH disruption led to an increased production and a defective differentiation of MΦ Prim progenitors. These differentiation defects were associated with profound modifications of the expression of genes involved in embryonic patterning and neurodevelopment. They also induced a reduced production of mature MΦ/microglia in the early brain, as well as a transient reduction of the microglia pool at midgestation and in the new-born.
We thus identify Lyl-1 as a critical regulator of MΦ Prim and microglia development, which disruption may impair organogenesis, including neurodevelopment processes.
Key points: 1-Lyl-1 expression marks yolk sac macrophages and brain macrophage/microglia/BAM. 2-Lyl-1 deficiency impairs primitive macrophage development and leads to the up-regulation of genes involved in embryo patterning. 3-Lyl-1-expressing primitive macrophages have an immuno-modulatory phenotype. 4-Lyl-1 deficiency impairs microglia development and the expression of genes involved in neuro-development.
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Dates et versions

hal-02992875 , version 1 (06-11-2020)

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Shoutang Wang, Deshan Ren, Anna-Lila Kaushik, Gabriel Matherat, Yann Lécluse, et al.. Lyl-1 marks and regulates primitive macrophages and microglia development. 2020. ⟨hal-02992875⟩
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