Notch Signaling Rescues Loss of Satellite Cells Lacking Pax7 and Promotes Brown Adipogenic Differentiation
Pax7 is a nodal transcription factor that is essential for regulating the maintenance, expansion, and myogenic identity of satellite cells during both neonatal and adult myogenesis. Deletion of Pax7 results in loss of satellite cells and impaired muscle regeneration. Here, we show that ectopic expre...
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| Format: | Article |
| Language: | English |
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Elsevier
2016-07-01
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| Series: | Cell Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124716307203 |
| _version_ | 1818694483183665152 |
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| author | Alessandra Pasut Natasha C. Chang Uxia Gurriaran Rodriguez Sharlene Faulkes Hang Yin Melanie Lacaria Hong Ming Michael A. Rudnicki |
| author_facet | Alessandra Pasut Natasha C. Chang Uxia Gurriaran Rodriguez Sharlene Faulkes Hang Yin Melanie Lacaria Hong Ming Michael A. Rudnicki |
| author_sort | Alessandra Pasut |
| collection | DOAJ |
| description | Pax7 is a nodal transcription factor that is essential for regulating the maintenance, expansion, and myogenic identity of satellite cells during both neonatal and adult myogenesis. Deletion of Pax7 results in loss of satellite cells and impaired muscle regeneration. Here, we show that ectopic expression of the constitutively active intracellular domain of Notch1 (NICD1) rescues the loss of Pax7-deficient satellite cells and restores their proliferative potential. Strikingly NICD1-expressing satellite cells do not undergo myogenic differentiation and instead acquire a brown adipogenic fate both in vivo and in vitro. NICD-expressing Pax7−/− satellite cells fail to upregulate MyoD and instead express the brown adipogenic marker PRDM16. Overall, these results show that Notch1 activation compensates for the loss of Pax7 in the quiescent state and acts as a molecular switch to promote brown adipogenesis in adult skeletal muscle. |
| first_indexed | 2024-12-17T13:30:17Z |
| format | Article |
| id | doaj.art-af7dbb4bd61f48078eca529bc2aaa1b9 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-17T13:30:17Z |
| publishDate | 2016-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-af7dbb4bd61f48078eca529bc2aaa1b92022-12-21T21:46:36ZengElsevierCell Reports2211-12472016-07-0116233334310.1016/j.celrep.2016.06.001Notch Signaling Rescues Loss of Satellite Cells Lacking Pax7 and Promotes Brown Adipogenic DifferentiationAlessandra Pasut0Natasha C. Chang1Uxia Gurriaran Rodriguez2Sharlene Faulkes3Hang Yin4Melanie Lacaria5Hong Ming6Michael A. Rudnicki7Sprott Center for Stem Cell Research, Ottawa Hospital Research Institute, Ottawa, ON K1H8L6, CanadaSprott Center for Stem Cell Research, Ottawa Hospital Research Institute, Ottawa, ON K1H8L6, CanadaSprott Center for Stem Cell Research, Ottawa Hospital Research Institute, Ottawa, ON K1H8L6, CanadaSprott Center for Stem Cell Research, Ottawa Hospital Research Institute, Ottawa, ON K1H8L6, CanadaSprott Center for Stem Cell Research, Ottawa Hospital Research Institute, Ottawa, ON K1H8L6, CanadaSprott Center for Stem Cell Research, Ottawa Hospital Research Institute, Ottawa, ON K1H8L6, CanadaSprott Center for Stem Cell Research, Ottawa Hospital Research Institute, Ottawa, ON K1H8L6, CanadaSprott Center for Stem Cell Research, Ottawa Hospital Research Institute, Ottawa, ON K1H8L6, CanadaPax7 is a nodal transcription factor that is essential for regulating the maintenance, expansion, and myogenic identity of satellite cells during both neonatal and adult myogenesis. Deletion of Pax7 results in loss of satellite cells and impaired muscle regeneration. Here, we show that ectopic expression of the constitutively active intracellular domain of Notch1 (NICD1) rescues the loss of Pax7-deficient satellite cells and restores their proliferative potential. Strikingly NICD1-expressing satellite cells do not undergo myogenic differentiation and instead acquire a brown adipogenic fate both in vivo and in vitro. NICD-expressing Pax7−/− satellite cells fail to upregulate MyoD and instead express the brown adipogenic marker PRDM16. Overall, these results show that Notch1 activation compensates for the loss of Pax7 in the quiescent state and acts as a molecular switch to promote brown adipogenesis in adult skeletal muscle.http://www.sciencedirect.com/science/article/pii/S2211124716307203Pax7Notch1NICD1satellite cellsmyogenicbrown adipogenic |
| spellingShingle | Alessandra Pasut Natasha C. Chang Uxia Gurriaran Rodriguez Sharlene Faulkes Hang Yin Melanie Lacaria Hong Ming Michael A. Rudnicki Notch Signaling Rescues Loss of Satellite Cells Lacking Pax7 and Promotes Brown Adipogenic Differentiation Cell Reports Pax7 Notch1 NICD1 satellite cells myogenic brown adipogenic |
| title | Notch Signaling Rescues Loss of Satellite Cells Lacking Pax7 and Promotes Brown Adipogenic Differentiation |
| title_full | Notch Signaling Rescues Loss of Satellite Cells Lacking Pax7 and Promotes Brown Adipogenic Differentiation |
| title_fullStr | Notch Signaling Rescues Loss of Satellite Cells Lacking Pax7 and Promotes Brown Adipogenic Differentiation |
| title_full_unstemmed | Notch Signaling Rescues Loss of Satellite Cells Lacking Pax7 and Promotes Brown Adipogenic Differentiation |
| title_short | Notch Signaling Rescues Loss of Satellite Cells Lacking Pax7 and Promotes Brown Adipogenic Differentiation |
| title_sort | notch signaling rescues loss of satellite cells lacking pax7 and promotes brown adipogenic differentiation |
| topic | Pax7 Notch1 NICD1 satellite cells myogenic brown adipogenic |
| url | http://www.sciencedirect.com/science/article/pii/S2211124716307203 |
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