造血
吞噬作用
干细胞
细胞生物学
DNA
块(置换群论)
生物
遗传学
几何学
数学
作者
Cecília Pessoa Rodrigues,Joseph M. Collins,Song Yang,Catherine Martinez,Ji Wook Kim,Chhiring Lama,Anna S. Nam,Clemens Alt,Charles P. Lin,Leonard I. Zon
出处
期刊:Science
[American Association for the Advancement of Science (AAAS)]
日期:2024-09-12
卷期号:385 (6714)
标识
DOI:10.1126/science.adn1629
摘要
Macrophages maintain hematopoietic stem cell (HSC) quality by assessing cell surface Calreticulin (Calr), an “eat-me” signal induced by reactive oxygen species (ROS). Using zebrafish genetics, we identified Beta-2-microglobulin (B2m) as a crucial “don’t eat-me” signal on blood stem cells. A chemical screen revealed inducers of surface Calr that promoted HSC proliferation without triggering ROS or macrophage clearance. Whole-genome CRISPR-Cas9 screening showed that Toll-like receptor 3 (Tlr3) signaling regulated b2m expression. Targeting b2m or tlr3 reduced the HSC clonality. Elevated B2m levels correlated with high expression of repetitive element (RE) transcripts. Overall, our data suggest that RE-associated double-stranded RNA could interact with TLR3 to stimulate surface expression of B2m on hematopoietic stem and progenitor cells. These findings suggest that the balance of Calr and B2m regulates macrophage-HSC interactions and defines hematopoietic clonality.
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