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

Animals Cell Differentiation Cells, Cultured Eye Proteins / metabolism Mice Mice, Inbred C57BL Mice, Knockout Muscle Development Muscle, Skeletal / physiology Nerve Growth Factors / metabolism Regeneration / genetics Satellite Cells, Skeletal Muscle / cytology Serpins / metabolism Signal Transduction Transcription Factors / genetics Transcriptome Tumor Suppressor Protein p53 / metabolism
NELF PEDF signaling muscle regeneration muscle stem cells nascent transcript stability p53 signaling promoter proximal pausing stem cell niche stem cell self-renewal transcriptional regulation

Journal

Developmental cell
ISSN: 1878-1551
Titre abrégé: Dev Cell
Pays: United States
ID NLM: 101120028

Informations de publication

Date de publication:
05 04 2021
Historique:
received: 30 04 2020
revised: 08 01 2021
accepted: 19 02 2021
pubmed: 19 3 2021
medline: 24 8 2021
entrez: 18 3 2021
Statut: ppublish

Résumé

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.

Identifiants

DOI: 10.1016/j.devcel.2021.02.025 PMID: 33735618 PMC: PMC8357161
pubmed: 33735618
pii: S1534-5807(21)00165-9
doi: 10.1016/j.devcel.2021.02.025
pmc: PMC8357161
mid: NIHMS1719832
pii:
doi:

Substances chimiques

Eye Proteins 0
Nerve Growth Factors 0
Serpins 0
Transcription Factors 0
Trp53 protein, mouse 0
Tumor Suppressor Protein p53 0
negative elongation factor 0
pigment epithelium-derived factor 0

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1014-1029.e7

Subventions

Organisme : NIAMS NIH HHS
ID : R01 AR044031
Pays : United States
Organisme : NLM NIH HHS
ID : T15 LM007092
Pays : United States
Organisme : CIHR
ID : FDN-143330
Pays : Canada
Organisme : CIHR
ID : MOP-343603
Pays : Canada

Informations de copyright

Copyright © 2021 Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests The authors declare no competing interests.

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Auteurs

Daniel C L Robinson (DCL)

Sprott Center for Stem Cell Research, Regenerative Medicine Program Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada; Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, ON K1H 8L6, Canada.

Morten Ritso (M)

Sprott Center for Stem Cell Research, Regenerative Medicine Program Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada.

Geoffrey M Nelson (GM)

Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA; Department of Biomedical Informatics, Harvard Medical School, Boston, MA 02115, USA.

Zeinab Mokhtari (Z)

Sprott Center for Stem Cell Research, Regenerative Medicine Program Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada; Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, ON K1H 8L6, Canada.

Kiran Nakka (K)

Sprott Center for Stem Cell Research, Regenerative Medicine Program Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada.

Hina Bandukwala (H)

Sprott Center for Stem Cell Research, Regenerative Medicine Program Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada.

Seth R Goldman (SR)

Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.

Peter J Park (PJ)

Department of Biomedical Informatics, Harvard Medical School, Boston, MA 02115, USA.

Rémi Mounier (R)

Institut NeuroMyoGène, Université Claude Bernard - Lyon 1, CNRS 5310, INSERM U1217, Lyon 69008, France.

Bénédicte Chazaud (B)

Institut NeuroMyoGène, Université Claude Bernard - Lyon 1, CNRS 5310, INSERM U1217, Lyon 69008, France.

Marjorie Brand (M)

Sprott Center for Stem Cell Research, Regenerative Medicine Program Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada; Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, ON K1H 8L6, Canada; LIFE Research Institute, University of Ottawa, Ottawa, ON K1H 8L6, Canada.

Michael A Rudnicki (MA)

Sprott Center for Stem Cell Research, Regenerative Medicine Program Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada; Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, ON K1H 8L6, Canada.

Karen Adelman (K)

Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.

F Jeffrey Dilworth (FJ)

Sprott Center for Stem Cell Research, Regenerative Medicine Program Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada; Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, ON K1H 8L6, Canada; LIFE Research Institute, University of Ottawa, Ottawa, ON K1H 8L6, Canada. Electronic address: jdilworth@ohri.ca.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Negative elongation factor regulates muscle...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Différenciation cellulaire › Negative elongation factor regulates muscle...
questionsmedicales.fr › Cellules › Cellules cultivées › Negative elongation factor regulates muscle...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines de l'oeil › Negative elongation factor regulates muscle...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Negative elongation factor regulates muscle...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Lignées consanguines de souris › Souris de lignée C57BL › Negative elongation factor regulates muscle...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Souris transgéniques › Souris knockout › Negative elongation factor regulates muscle...
questionsmedicales.fr › Phénomènes physiologiques de l'appareil locomoteur et du système nerveux › Phénomènes physiologiques du système locomoteur › Développement locomoteur › Développement musculaire › Negative elongation factor regulates muscle...
questionsmedicales.fr › Tissus › Muscles › Muscle strié › Muscles squelettiques › Negative elongation factor regulates muscle...
questionsmedicales.fr › Facteurs biologiques › Protéines et peptides de signalisation intercellulaire › Facteurs de croissance nerveuse › Negative elongation factor regulates muscle...
questionsmedicales.fr › Phénomènes biologiques › Régénération › Negative elongation factor regulates muscle...
questionsmedicales.fr › Cellules › Cellules souches › Myoblastes › Myoblastes squelettiques › Cellules satellites du muscle squelettique › Negative elongation factor regulates muscle...
questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Mécanismes moléculaires de l'action pharmacologique › Antienzymes › Inhibiteurs de protéases › Inhibiteurs de la sérine protéinase › Serpines › Negative elongation factor regulates muscle...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Transduction du signal › Negative elongation factor regulates muscle...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Facteurs de transcription › Negative elongation factor regulates muscle...
questionsmedicales.fr › Phénomènes génétiques › Structures génétiques › Transcriptome › Negative elongation factor regulates muscle...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Phosphoprotéines › Protéine p53 suppresseur de tumeur › Negative elongation factor regulates muscle...