German researchers have revealed new insights into haematopoietic regeneration after chemotherapy.
In response to stress such as chemotherapy, haematopoietic stem cells (HSCs) leave their usual state of 'quiescence' in order to differentiate and repopulate the blood supply. However, the way in which inflammation is activated in HSCs after stress is not fully understood. Researchers led by Dr Thomas Clapes of the Max Planck Institute of Immunobiology and Epigenetics therefore decided to study this process.
They found that during haematopoietic regeneration after chemotherapy, the innate immune receptor MDA5 was activated by increased expression of transposable elements.
Transposable elements are genetic remnants of bacteria and viruses that have integrated into the human genome over millions of years of evolution.
MDA5 induces inflammation by triggering an inflammatory response that is necessary for HSCs to exit quiescence and proliferate.
In Nature Cell Biology last week, they write: “Our findings show that transposable elements are transcriptionally upregulated after chemotherapy and act as ligands for MDA5 to trigger an inflammatory response that results in HSCs exiting quiescence.
“Our findings are consistent with previous research showing that transposable elements are upregulated in HSCs after irradiation.”
They add that several other stress signals, including ageing, also activate transposable element expression. “Thus, it is plausible that transposable elements sensing by RNA/DNA sensors is a phenomenon that is used by diverse cell populations to respond to challenges.”
Co-author Dr Eirini Trompouki commented: “It is interesting to think that cells make use of transposable elements or other repetitive RNAs to finetune and adapt whenever they need to change their state, for example after stress.”
Clapes T, Polyzou A, Prater P, Sagar, Morales-Hernández A, Ferrarini MG, Kehrer N, Lefkopoulos S, Bergo V, Hummel B, Obier N, Maticzka D, Bridgeman A, Herman JS, Ilik I, Klaeylé L, Rehwinkel J, McKinney-Freeman S, Backofen R, Akhtar A, Cabezas-Wallscheid N, Sawarkar R, Rebollo R, Grün D, Trompouki E. (2021) “Chemotherapy-induced transposable elements activate MDA5 to enhance haematopoietic regeneration.” Nature Cell Biology, doi: 10.1038/s41556-021-00707-9
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