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Lyl-1 regulates primitive macrophages and microglia development. | LitMetric

AI Article Synopsis

  • Macrophage populations in the Yolk Sac develop from distinct progenitor waves before hematopoietic stem cells form, contributing to primitive macrophages in embryonic organs.
  • Lyl-1, a transcription factor, is shown to be crucial for the development and differentiation of these macrophage progenitors, with its deficiency leading to disruptions in gene regulation related to embryonic patterns and neurodevelopment.
  • The lack of Lyl-1 results in an initial increase of primitive macrophage progenitors, followed by compromised development of mature macrophages and microglia in the brain during crucial stages of early growth.

Article Abstract

During ontogeny, macrophage populations emerge in the Yolk Sac (YS) via two distinct progenitor waves, prior to hematopoietic stem cell development. Macrophage progenitors from the primitive/"early EMP" and transient-definitive/"late EMP" waves both contribute to various resident primitive macrophage populations in the developing embryonic organs. Identifying factors that modulates early stages of macrophage progenitor development may lead to a better understanding of defective function of specific resident macrophage subsets. Here we show that YS primitive macrophage progenitors express Lyl-1, a bHLH transcription factor related to SCL/Tal-1. Transcriptomic analysis of YS macrophage progenitors indicate that primitive macrophage progenitors present at embryonic day 9 are clearly distinct from those present at later stages. Disruption of Lyl-1 basic helix-loop-helix domain leads initially to an increased emergence of primitive macrophage progenitors, and later to their defective differentiation. These defects are associated with a disrupted expression of gene sets related to embryonic patterning and neurodevelopment. Lyl-1-deficiency also induce a reduced production of mature macrophages/microglia in the early brain, as well as a transient reduction of the microglia pool at midgestation and in the newborn. We thus identify Lyl-1 as a critical regulator of primitive macrophages and microglia development, which disruption may impair resident-macrophage function during organogenesis.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8660792PMC
http://dx.doi.org/10.1038/s42003-021-02886-5DOI Listing

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