@Article{Clapes_Polyzou_Prater-Chemo_trans_eleme-2021,
  author =	 {Clapes, Thomas and Polyzou, Aikaterini and Prater, Pia and 
                  Sagar and Morales-Hernandez, Antonio and Ferrarini, Mariana 
                  Galvao and Kehrer, Natalie and Lefkopoulos, Stylianos and 
                  Bergo, Veronica and Hummel, Barbara and Obier, Nadine and 
                  Maticzka, Daniel and Bridgeman, Anne and Herman, Josip S. 
                  and Ilik, Ibrahim and Klaeyle, Lheanna and Rehwinkel, Jan 
                  and McKinney-Freeman, Shannon and Backofen, Rolf and Akhtar, 
                  Asifa and Cabezas-Wallscheid, Nina and Sawarkar, Ritwick and 
                  Rebollo, Rita and Grun, Dominic and Trompouki, Eirini},
  title =	 {Chemotherapy-induced transposable elements activate {MDA5} 
                  to enhance haematopoietic regeneration},
  journal =	 {Nat Cell Biol},
  year =	 {2021},
  volume =	 {23},
  number =	 {7},
  pages =	 {704-717},
  user =	 {backofen},
  pmid =	 {34253898},
  doi = 	 {10.1038/s41556-021-00707-9},
  issn = 	 {1476-4679},
  issn = 	 {1465-7392},
  abstract =	 {Haematopoietic stem cells (HSCs) are normally quiescent, 
                  but have evolved mechanisms to respond to stress. Here, we 
                  evaluate haematopoietic regeneration induced by 
                  chemotherapy. We detect robust chromatin reorganization 
                  followed by increased transcription of transposable elements 
                  (TEs) during early recovery. TE transcripts bind to and 
                  activate the innate immune receptor melanoma 
                  differentiation-associated protein 5 (MDA5) that generates 
                  an inflammatory response that is necessary for HSCs to exit 
                  quiescence. HSCs that lack MDA5 exhibit an impaired 
                  inflammatory response after chemotherapy and retain their 
                  quiescence, with consequent better long-term repopulation 
                  capacity. We show that the overexpression of ERV and LINE 
                  superfamily TE copies in wild-type HSCs, but not in 
                  Mda5(-/-) HSCs, results in their cycling. By contrast, after 
                  knockdown of LINE1 family copies, HSCs retain their 
                  quiescence. Our results show that TE transcripts act as 
                  ligands that activate MDA5 during haematopoietic 
                  regeneration, thereby enabling HSCs to mount an inflammatory 
                  response necessary for their exit from quiescence.}
}