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

Lefkopoulos, S., Polyzou, A., Derecka, M., Bergo, V., Clapes, T., Cauchy, P., et al. (2020). Repetitive Elements Trigger RIG-I-like Receptor Signaling that Regulates the emergence of Hematopoietic Stem and Progenitor Cells. Immunity, 53, 934-951. doi:10.1016/j.immuni.2020.10.007.

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Lefkopoulos, Stylianos1, Author
Polyzou, Aikaterini1, Author
Derecka, Marta1, Author
Bergo, Veronica1, Author
Clapes, Thomas1, Author
Cauchy, Pierre1, Author              
Jerez-Longres, Carolina1, Author
Onishi-Seebacher, Megumi2, Author
Yin, Na1, Author
Martagon-Calderón, Natalia-Adriana1, Author
Potts, Kathryn S.2, Author
Klaeylé, Lhéanna1, Author
Liu, Feng2, Author
Bowman, Teresa V.2, Author
Jenuwein, Thomas3, Author              
Mione, Maria Caterina2, Author
Trompouki, Eirini1, Author              
Affiliations:
1Department of Cellular and Molecular Immunology, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society, ou_2243641              
2External Organizations, ou_persistent22              
3Department of Epigenetics, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society, ou_2243644              

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 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 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.

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Language(s): eng - English
 Dates: 2020-11-17
 Publication Status: Published in print
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 Rev. Type: Peer
 Identifiers: DOI: 10.1016/j.immuni.2020.10.007
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Title: Immunity
Source Genre: Journal
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Publ. Info: Cambridge, Mass. : Cell Press
Pages: - Volume / Issue: 53 Sequence Number: - Start / End Page: 934 - 951 Identifier: ISSN: 1074-7613
CoNE: https://pure.mpg.de/cone/journals/resource/954925604783