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Journal Article

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

MPS-Authors

Lefkopoulos,  Stylianos
Department of Cellular and Molecular Immunology, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Polyzou,  Aikaterini
Department of Cellular and Molecular Immunology, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Derecka,  Marta
Department of Cellular and Molecular Immunology, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Bergo,  Veronica
Department of Cellular and Molecular Immunology, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Clapes,  Thomas
Department of Cellular and Molecular Immunology, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

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Cauchy,  Pierre
Department of Cellular and Molecular Immunology, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Jerez-Longres,  Carolina
Department of Cellular and Molecular Immunology, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Yin,  Na
Department of Cellular and Molecular Immunology, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Martagon-Calderón,  Natalia-Adriana
Department of Cellular and Molecular Immunology, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Klaeylé,  Lhéanna
Department of Cellular and Molecular Immunology, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

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Jenuwein,  Thomas
Department of Epigenetics, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

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Trompouki,  Eirini
Department of Cellular and Molecular Immunology, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Fulltext (public)

Lefkopoulos et al. 2020.pdf
(Publisher version), 6MB

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Citation

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.


Cite as: http://hdl.handle.net/21.11116/0000-0007-672D-4
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.