Repetitive Elements Trigger RIG-I-like Receptor Signaling that Regulates the Emergence of Hematopoietic Stem and Progenitor Cells
| Autor: | Natalia Adriana Martagon-Calderón, Aikaterini Polyzou, Na Yin, Veronica Bergo, Marta Derecka, Eirini Trompouki, Feng Liu, Stylianos Lefkopoulos, Kathryn S. Potts, Lhéanna Klaeylé, Thomas Clapes, Thomas Jenuwein, Pierre Cauchy, Teresa V. Bowman, Maria Caterina Mione, Megumi Onishi-Seebacher, Carolina Jerez-Longres |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Immunology Inflammation Biology RIG-I-like receptor 03 medical and health sciences 0302 clinical medicine medicine Animals Immunology and Allergy Progenitor cell Receptor Zebrafish Repetitive Sequences Nucleic Acid TNF Receptor-Associated Factor 6 Valproic Acid Gene Expression Regulation Developmental RNA-Binding Proteins MDA5 Zebrafish Proteins Chromatin Assembly and Disassembly Hematopoietic Stem Cells biology.organism_classification Immunohistochemistry Immunity Innate Hematopoiesis Cell biology Haematopoiesis 030104 developmental biology Infectious Diseases 030220 oncology & carcinogenesis DNA Transposable Elements Ectopic expression Disease Susceptibility medicine.symptom Biomarkers RNA Helicases Signal Transduction |
| Zdroj: | Immunity |
| ISSN: | 1074-7613 |
| DOI: | 10.1016/j.immuni.2020.10.007 |
| Popis: | Inflammatory signaling is required for hematopoietic stem and progenitor cell (HSPC) development. Here, we studied the involvement of RIG-I-like receptors (RLRs) in HSPC formation. Rig-I or Mda5 deficiency impaired, while Lgp2 deficiency enhanced, HSPC emergence in zebrafish embryos. Rig-I or Mda5 deficiency reduced HSPC numbers by inhibiting inflammatory signals that were in turn enhanced in Lgp2 deficient embryos. Simultaneous reduction 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 embryos restored HSPC numbers. Repetitive element transcripts could be detected in hemogenic endothelial cells and HSPCs, suggesting a role as RLR ligands. Indeed, ectopic expression of repetitive elements enhanced HSPC formation in wild-type, but not in Rig-I or Mda5 deficient embryos. Manipulation of RLR expression in mouse fetal liver HSPCs indicated functional conservation among species. Thus, repetitive elements transcribed during development drive RLR-mediated inflammatory signals that regulate HSPC formation. |
| Databáze: | OpenAIRE |
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