FOS licenses early events in stem cell activation driving skeletal muscle regeneration
| Autor: | Naftali Horwitz, Feodor D. Price, Lee L. Rubin, Amy J. Wagers, Michelle Ko, Özge Vargel Bölükbaşı, Manisha Sinha, Alfredo E. Gonzalez, Sonia Chen, A. Almada, Kathleen A. Messemer |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Satellite Cells Skeletal Muscle Biology General Biochemistry Genetics and Molecular Biology 03 medical and health sciences Mice 0302 clinical medicine medicine Animals Progenitor cell Muscle Skeletal Cells Cultured Cell Proliferation Messenger RNA Oncogene Regeneration (biology) Stem Cells Skeletal muscle Genes fos Cell migration Cell cycle Cell biology 030104 developmental biology medicine.anatomical_structure Stem cell Proto-Oncogene Proteins c-fos 030217 neurology & neurosurgery |
| Zdroj: | Cell reports. 34(4) |
| ISSN: | 2211-1247 |
| Popis: | Muscle satellite cells (SCs) are a quiescent (non-proliferative) stem cell population in uninjured skeletal muscle. Although SCs have been investigated for nearly 60 years, the molecular drivers that transform quiescent SCs into the rapidly dividing (activated) stem/progenitor cells that mediate muscle repair after injury remain largely unknown. Here we identify a prominent FBJ osteosarcoma oncogene (Fos) mRNA and protein signature in recently activated SCs that is rapidly, heterogeneously, and transiently induced by muscle damage. We further reveal a requirement for FOS to efficiently initiate key stem cell functions, including cell cycle entry, proliferative expansion, and muscle regeneration, via induction of "pro-regenerative" target genes that stimulate cell migration, division, and differentiation. Disruption of one of these Fos/AP-1 targets, NAD(+)-consuming mono-ADP-ribosyl-transferase 1 (Art1), in SCs delays cell cycle entry and impedes progenitor cell expansion and muscle regeneration. This work uncovers an early-activated FOS/ART1/mono-ADP-ribosylation (MARylation) pathway that is essential for stem cell-regenerative responses. |
| Databáze: | OpenAIRE |
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