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

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 re

SUBMITTER: Robinson DCL 

PROVIDER: S-EPMC8357161 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature