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Notch Signaling Rescues Loss of Satellite Cells Lacking Pax7 and Promotes Brown Adipogenic Differentiation.
Cell Rep. 2016 07 12; 16(2):333-343.CR

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+Show Affiliations

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.Sprott Center for Stem Cell Research, Ottawa Hospital Research Institute, Ottawa, ON K1H8L6, Canada.Sprott Center for Stem Cell Research, Ottawa Hospital Research Institute, Ottawa, ON K1H8L6, Canada.Sprott Center for Stem Cell Research, Ottawa Hospital Research Institute, Ottawa, ON K1H8L6, Canada.Sprott Center for Stem Cell Research, Ottawa Hospital Research Institute, Ottawa, ON K1H8L6, Canada.Sprott Center for Stem Cell Research, Ottawa Hospital Research Institute, Ottawa, ON K1H8L6, Canada.Sprott Center for Stem Cell Research, Ottawa Hospital Research Institute, Ottawa, ON K1H8L6, Canada.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.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

27346341

Citation

Pasut, Alessandra, et al. "Notch Signaling Rescues Loss of Satellite Cells Lacking Pax7 and Promotes Brown Adipogenic Differentiation." Cell Reports, vol. 16, no. 2, 2016, pp. 333-343.
Pasut A, Chang NC, Gurriaran-Rodriguez U, et al. Notch Signaling Rescues Loss of Satellite Cells Lacking Pax7 and Promotes Brown Adipogenic Differentiation. Cell Rep. 2016;16(2):333-343.
Pasut, A., Chang, N. C., Gurriaran-Rodriguez, U., Faulkes, S., Yin, H., Lacaria, M., Ming, H., & Rudnicki, M. A. (2016). Notch Signaling Rescues Loss of Satellite Cells Lacking Pax7 and Promotes Brown Adipogenic Differentiation. Cell Reports, 16(2), 333-343. https://doi.org/10.1016/j.celrep.2016.06.001
Pasut A, et al. Notch Signaling Rescues Loss of Satellite Cells Lacking Pax7 and Promotes Brown Adipogenic Differentiation. Cell Rep. 2016 07 12;16(2):333-343. PubMed PMID: 27346341.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Notch Signaling Rescues Loss of Satellite Cells Lacking Pax7 and Promotes Brown Adipogenic Differentiation. AU - Pasut,Alessandra, AU - Chang,Natasha C, AU - Gurriaran-Rodriguez,Uxia, AU - Faulkes,Sharlene, AU - Yin,Hang, AU - Lacaria,Melanie, AU - Ming,Hong, AU - Rudnicki,Michael A, Y1 - 2016/06/23/ PY - 2014/10/19/received PY - 2016/04/22/revised PY - 2016/05/21/accepted PY - 2016/6/28/entrez PY - 2016/6/28/pubmed PY - 2017/12/2/medline KW - NICD1 KW - Notch1 KW - Pax7 KW - brown adipogenic KW - myogenic KW - satellite cells SP - 333 EP - 343 JF - Cell reports JO - Cell Rep VL - 16 IS - 2 N2 - 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. SN - 2211-1247 UR - https://www.unboundmedicine.com/medline/citation/27346341/Notch_Signaling_Rescues_Loss_of_Satellite_Cells_Lacking_Pax7_and_Promotes_Brown_Adipogenic_Differentiation_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S2211-1247(16)30720-3 DB - PRIME DP - Unbound Medicine ER -