title: Notch Signaling Rescues Loss of Satellite Cells Lacking Pax7 and Promotes Brown Adipogenic Differentiation.
abstract: 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.
authors.affiliation: Sprott Center for Stem Cell Research, Ottawa Hospital Research Institute, Ottawa, ON K1H8L6, Canada; Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H8M5, Canada.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Pasut
authors.affiliation: Sprott Center for Stem Cell Research, Ottawa Hospital Research Institute, Ottawa, ON K1H8L6, Canada.
authors.forename: Natasha C
authors.initials: NC
authors.lastname: Chang
authors.affiliation: Sprott Center for Stem Cell Research, Ottawa Hospital Research Institute, Ottawa, ON K1H8L6, Canada.
authors.forename: Uxia
authors.initials: U
authors.lastname: Gurriaran-Rodriguez
authors.affiliation: Sprott Center for Stem Cell Research, Ottawa Hospital Research Institute, Ottawa, ON K1H8L6, Canada.
authors.forename: Sharlene
authors.initials: S
authors.lastname: Faulkes
authors.affiliation: Sprott Center for Stem Cell Research, Ottawa Hospital Research Institute, Ottawa, ON K1H8L6, Canada.
authors.forename: Hang
authors.initials: H
authors.lastname: Yin
authors.affiliation: Sprott Center for Stem Cell Research, Ottawa Hospital Research Institute, Ottawa, ON K1H8L6, Canada.
authors.forename: Melanie
authors.initials: M
authors.lastname: Lacaria
authors.affiliation: Sprott Center for Stem Cell Research, Ottawa Hospital Research Institute, Ottawa, ON K1H8L6, Canada.
authors.forename: Hong
authors.initials: H
authors.lastname: Ming
authors.affiliation: Sprott Center for Stem Cell Research, Ottawa Hospital Research Institute, Ottawa, ON K1H8L6, Canada; Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H8M5, Canada. Electronic address: mrudnicki@ohri.ca.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Rudnicki
mesh_terms: D050156:Adipogenesis; D002001:Adipose Tissue, Brown / Q000166:cytology / Q000502:physiology; D000818:Animals; D002478:Cells, Cultured; D008822:Mice, Transgenic; D017570:MyoD Protein / Q000378:metabolism; D051763:PAX7 Transcription Factor / Q000235:genetics* / Q000378:metabolism; D051881:Receptor, Notch1 / Q000235:genetics / Q000378:metabolism; D032496:Satellite Cells, Skeletal Muscle / Q000502:physiology*; D015398:Signal Transduction
chemical_list: D017570:MyoD Protein; C057363:MyoD1 myogenic differentiation protein; C497762:Notch1 protein, mouse; D051763:PAX7 Transcription Factor; C497322:Pax7 protein, mouse; D051881:Receptor, Notch1
keywords: NICD1; Notch1; Pax7; brown adipogenic; myogenic; satellite cells