Tissue damage and senescence provide critical signals for cellular reprogramming in vivo

TLDR

Cell reprogramming can convert differentiated cells into new identities by expressing four transcription factors, a process that holds promise for therapeutic tissue regeneration. The authors employed a mouse model to investigate the in vivo signals that drive cellular reprogramming. They discovered that the same factors that induce reprogramming in vitro also act in vivo but cause cellular damage, leading senescent cells to secrete interleukin‑6 and other factors that create a tissue environment conducive to reprogramming neighboring cells. Mosteiro et al., Science, DOI 10.1126/science.aaf4445.

Abstract

For cell reprogramming, context matters Differentiated cells in a culture dish can assume a new identity when manipulated to express four transcription factors. This “reprogramming” process has sparked interest because conceivably it could be harnessed as a therapeutic strategy for tissue regeneration. Mosteiro et al. used a mouse model to study the signals that promote cell reprogramming in vivo. They found that the factors that trigger reprogramming in vitro do the same in vivo; however, they also inflict cell damage. The damaged cells enter a state of senescence and begin secreting certain factors that promote reprogramming, including an inflammatory cytokine called interleukin-6. Thus, in the physiological setting, cell senescence may create a tissue context that favors reprogramming of neighboring cells. Science , this issue p. 10.1126/science.aaf4445