Negative Elongation Factor Regulates Muscle Progenitor Expansion for Efficient Myofiber Repair and Stem Cell Pool Repopulation

Overview

Journal Dev Cell

Publisher Cell Press

Specialties Cell Biology
Reproductive Medicine

Date 2021 Mar 18

PMID 33735618

Citations 14

Authors

Daniel C L Robinson

Morten Ritso

Geoffrey M Nelson

Zeinab Mokhtari

Kiran Nakka

Hina Bandukwala

Seth R Goldman

Peter J Park

Remi Mounier

Benedicte Chazaud

Marjorie Brand

Michael A Rudnicki

Karen Adelman

F Jeffrey Dilworth

Affiliations

Soon will be listed here.

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.

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