Negative elongation factor regulates muscle progenitor expansion for efficient myofiber repair and stem cell pool repopulation

Citation:

Robinson DCL, Ritso M, Nelson GM, Mokhtari Z, Nakka K, Bandukwala H, Goldman SR, Park PJ, Mounier R, Chazaud B, Brand M, Rudnicki MA, Adelman K, Dilworth JF. Negative elongation factor regulates muscle progenitor expansion for efficient myofiber repair and stem cell pool repopulation. Dev Cell 2021;56(7):1014-1029.e7. Copy at http://www.tinyurl.com/yfdzetbe

Date Published:

2021 04 05

Abstract:

Negative elongation factor (NELF) is a critical transcriptional regulator that stabilizes paused RNA polymerase to permit rapid gene expression changes in response to environmental cues. Although NELF is essential for embryonic development, its role in adult stem cells remains unclear. In this study, through a muscle-stem-cell-specific deletion, we showed that NELF is required for efficient muscle regeneration and stem cell pool replenishment. In mechanistic studies using PRO-seq, single-cell trajectory analyses and myofiber cultures revealed that NELF works at a specific stage of regeneration whereby it modulates p53 signaling to permit massive expansion of muscle progenitors. Strikingly, transplantation experiments indicated that these progenitors are also necessary for stem cell pool repopulation, implying that they are able to return to quiescence. Thus, we identified a critical role for NELF in the expansion of muscle progenitors in response to injury and revealed that progenitors returning to quiescence are major contributors to the stem cell pool repopulation.

Last updated on 09/14/2021