PRMT7 Preserves Satellite Cell Regenerative Capacity
Regeneration of skeletal muscle requires the continued presence of quiescent muscle stem cells (satellite cells), which become activated in response to injury. Here, we report that whole-body protein arginine methyltransferase PRMT7−/− adult mice and mice conditionally lacking PRMT7 in satellite cel...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2016-02-01
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| Series: | Cell Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124716000437 |
| _version_ | 1811305573640044544 |
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| author | Roméo Sébastien Blanc Gillian Vogel Taiping Chen Colin Crist Stéphane Richard |
| author_facet | Roméo Sébastien Blanc Gillian Vogel Taiping Chen Colin Crist Stéphane Richard |
| author_sort | Roméo Sébastien Blanc |
| collection | DOAJ |
| description | Regeneration of skeletal muscle requires the continued presence of quiescent muscle stem cells (satellite cells), which become activated in response to injury. Here, we report that whole-body protein arginine methyltransferase PRMT7−/− adult mice and mice conditionally lacking PRMT7 in satellite cells using Pax7-CreERT2 both display a significant reduction in satellite cell function, leading to defects in regenerative capacity upon muscle injury. We show that PRMT7 is preferentially expressed in activated satellite cells and, interestingly, PRMT7-deficient satellite cells undergo cell-cycle arrest and premature cellular senescence. These defects underlie poor satellite cell stem cell capacity to regenerate muscle and self-renew after injury. PRMT7-deficient satellite cells express elevated levels of the CDK inhibitor p21CIP1 and low levels of its repressor, DNMT3b. Restoration of DNMT3b in PRMT7-deficient cells rescues PRMT7-mediated senescence. Our findings define PRMT7 as a regulator of the DNMT3b/p21 axis required to maintain muscle stem cell regenerative capacity. |
| first_indexed | 2024-04-13T08:27:54Z |
| format | Article |
| id | doaj.art-5eee86caacdd4041ad009fbf66ccabd4 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-04-13T08:27:54Z |
| publishDate | 2016-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-5eee86caacdd4041ad009fbf66ccabd42022-12-22T02:54:21ZengElsevierCell Reports2211-12472016-02-011461528153910.1016/j.celrep.2016.01.022PRMT7 Preserves Satellite Cell Regenerative CapacityRoméo Sébastien Blanc0Gillian Vogel1Taiping Chen2Colin Crist3Stéphane Richard4Terry Fox Molecular Oncology Group and Bloomfield Center for Research on Aging, Lady Davis Institute for Medical Research, Sir Mortimer B. Davis Jewish General Hospital, Montréal, QC H3T 1E2, CanadaTerry Fox Molecular Oncology Group and Bloomfield Center for Research on Aging, Lady Davis Institute for Medical Research, Sir Mortimer B. Davis Jewish General Hospital, Montréal, QC H3T 1E2, CanadaDepartment of Molecular Carcinogenesis and Center for Cancer Epigenetics, The University of Texas MD Anderson Cancer Center, Science Park, Smithville, TX 78957, USATerry Fox Molecular Oncology Group and Bloomfield Center for Research on Aging, Lady Davis Institute for Medical Research, Sir Mortimer B. Davis Jewish General Hospital, Montréal, QC H3T 1E2, CanadaTerry Fox Molecular Oncology Group and Bloomfield Center for Research on Aging, Lady Davis Institute for Medical Research, Sir Mortimer B. Davis Jewish General Hospital, Montréal, QC H3T 1E2, CanadaRegeneration of skeletal muscle requires the continued presence of quiescent muscle stem cells (satellite cells), which become activated in response to injury. Here, we report that whole-body protein arginine methyltransferase PRMT7−/− adult mice and mice conditionally lacking PRMT7 in satellite cells using Pax7-CreERT2 both display a significant reduction in satellite cell function, leading to defects in regenerative capacity upon muscle injury. We show that PRMT7 is preferentially expressed in activated satellite cells and, interestingly, PRMT7-deficient satellite cells undergo cell-cycle arrest and premature cellular senescence. These defects underlie poor satellite cell stem cell capacity to regenerate muscle and self-renew after injury. PRMT7-deficient satellite cells express elevated levels of the CDK inhibitor p21CIP1 and low levels of its repressor, DNMT3b. Restoration of DNMT3b in PRMT7-deficient cells rescues PRMT7-mediated senescence. Our findings define PRMT7 as a regulator of the DNMT3b/p21 axis required to maintain muscle stem cell regenerative capacity.http://www.sciencedirect.com/science/article/pii/S2211124716000437PRMT7muscle regenerationsenescenceagingDNMT3bp21CIP1muscle stem cell |
| spellingShingle | Roméo Sébastien Blanc Gillian Vogel Taiping Chen Colin Crist Stéphane Richard PRMT7 Preserves Satellite Cell Regenerative Capacity Cell Reports PRMT7 muscle regeneration senescence aging DNMT3b p21CIP1 muscle stem cell |
| title | PRMT7 Preserves Satellite Cell Regenerative Capacity |
| title_full | PRMT7 Preserves Satellite Cell Regenerative Capacity |
| title_fullStr | PRMT7 Preserves Satellite Cell Regenerative Capacity |
| title_full_unstemmed | PRMT7 Preserves Satellite Cell Regenerative Capacity |
| title_short | PRMT7 Preserves Satellite Cell Regenerative Capacity |
| title_sort | prmt7 preserves satellite cell regenerative capacity |
| topic | PRMT7 muscle regeneration senescence aging DNMT3b p21CIP1 muscle stem cell |
| url | http://www.sciencedirect.com/science/article/pii/S2211124716000437 |
| work_keys_str_mv | AT romeosebastienblanc prmt7preservessatellitecellregenerativecapacity AT gillianvogel prmt7preservessatellitecellregenerativecapacity AT taipingchen prmt7preservessatellitecellregenerativecapacity AT colincrist prmt7preservessatellitecellregenerativecapacity AT stephanerichard prmt7preservessatellitecellregenerativecapacity |