德国马克斯普朗克免疫生物学和表观遗传学研究所的Eirini Trompouki研究组合作取得最新进展。他们发现重复元件触发RIG-I样受体信号，以调节造血干细胞和祖细胞（HSPC）的形成。这一研究成果于2020年11月6日发表在《免疫》杂志上。

他们研究了RIG-I样受体（RLRs）在HSPC形成中的作用。当Rig-I或Mda5缺陷减弱，而Lgp2缺陷增强，HSPC则在斑马鱼胚胎中出现。Rig-1或Mda5缺陷通过抑制炎症信号而降低HSPC数量，而炎症信号又在Lgp2缺乏的胚胎中得到增强。同时降低Lgp2和Rig-1或Mda5可挽救炎症信号和HSPC数量。

调节RLR缺陷型胚胎中信号传导介质Traf6的表达可恢复HSPC数量。可以在造血内皮细胞和HSPCs中检测到重复的元件转录本，表明其具有RLR的配体功能。实际上，在野生型中异位表达重复元件可增强HSPC的形成，但在Rig-1或Mda5缺陷型胚胎中则不会。小鼠胎肝HSPCs中RLR表达的操纵表明物种之间的功能保守。因此，在发育过程中转录的重复元件驱动RLR介导的炎症信号，以调节HSPC形成。

附：英文原文

Title: Repetitive Elements Trigger RIG-I-like Receptor Signaling that Regulates the Emergence of Hematopoietic Stem and Progenitor Cells

Author: Stylianos Lefkopoulos, Aikaterini Polyzou, Marta Derecka, Veronica Bergo, Thomas Clapes, Pierre Cauchy, Carolina Jerez-Longres, Megumi Onishi-Seebacher, Na Yin, Natalia-Adriana Martagon-Calderón, Kathryn S. Potts, Lhéanna Klaeylé, Feng Liu, Teresa V. Bowman, Thomas Jenuwein, Maria Caterina Mione, Eirini Trompouki

Issue&Volume: 2020-11-06

Abstract: Inflammatory signaling is required for hematopoietic stem and progenitor cell (HSPC)development. Here, we studied the involvement of RIG-I-like receptors (RLRs) in HSPCformation. Rig-I or Mda5 deficiency impaired, while Lgp2 deficiency enhanced, HSPCemergence in zebrafish embryos. Rig-I or Mda5 deficiency reduced HSPC numbers by inhibitinginflammatory signals that were in turn enhanced in Lgp2 deficient embryos. Simultaneousreduction of Lgp2 and either Rig-I or Mda5 rescued inflammatory signals and HSPC numbers.Modulating the expression of the signaling mediator Traf6 in RLR deficient embryosrestored HSPC numbers. Repetitive element transcripts could be detected in hemogenicendothelial cells and HSPCs, suggesting a role as RLR ligands. Indeed, ectopic expressionof repetitive elements enhanced HSPC formation in wild-type, but not in Rig-I or Mda5deficient embryos. Manipulation of RLR expression in mouse fetal liver HSPCs indicatedfunctional conservation among species. Thus, repetitive elements transcribed duringdevelopment drive RLR-mediated inflammatory signals that regulate HSPC formation.

DOI: 10.1016/j.immuni.2020.10.007

Source: https://www.cell.com/immunity/fulltext/S1074-7613(20)30448-9