@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},
doi = {10.1038/s41556-021-00707-9},
volume = {23},
user = {backofen},
pmid = {34253898},
pages = {704-717},
number = {7},
issn = {1476-4679},
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.}
}