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Constitutive Notch activation upregulates Pax7 and promotes the self-renewal of skeletal muscle satellite cells.
Mol Cell Biol. 2012 Jun; 32(12):2300-11.MC

Abstract

Notch signaling is a conserved cell fate regulator during development and postnatal tissue regeneration. Using skeletal muscle satellite cells as a model and through myogenic cell lineage-specific NICD(OE) (overexpression of constitutively activated Notch 1 intracellular domain), here we investigate how Notch signaling regulates the cell fate choice of muscle stem cells. We show that in addition to inhibiting MyoD and myogenic differentiation, NICD(OE) upregulates Pax7 and promotes the self-renewal of satellite cell-derived primary myoblasts in culture. Using MyoD(-/-) myoblasts, we further show that NICD(OE) upregulates Pax7 independently of MyoD inhibition. In striking contrast to previous observations, NICD(OE) also inhibits S-phase entry and Ki67 expression and thus reduces the proliferation of primary myoblasts. Overexpression of canonical Notch target genes mimics the inhibitory effects of NICD(OE) on MyoD and Ki67 but not the stimulatory effect on Pax7. Instead, NICD regulates Pax7 through interaction with RBP-Jκ, which binds to two consensus sites upstream of the Pax7 gene. Importantly, satellite cell-specific NICD(OE) results in impaired regeneration of skeletal muscles along with increased Pax7(+) mononuclear cells. Our results establish a role of Notch signaling in actively promoting the self-renewal of muscle stem cells through direct regulation of Pax7.

Authors+Show Affiliations

Department of Animal Sciences, Purdue University, West Lafayette, Indiana, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

Language

eng

PubMed ID

22493066

Citation

Wen, Yefei, et al. "Constitutive Notch Activation Upregulates Pax7 and Promotes the Self-renewal of Skeletal Muscle Satellite Cells." Molecular and Cellular Biology, vol. 32, no. 12, 2012, pp. 2300-11.
Wen Y, Bi P, Liu W, et al. Constitutive Notch activation upregulates Pax7 and promotes the self-renewal of skeletal muscle satellite cells. Mol Cell Biol. 2012;32(12):2300-11.
Wen, Y., Bi, P., Liu, W., Asakura, A., Keller, C., & Kuang, S. (2012). Constitutive Notch activation upregulates Pax7 and promotes the self-renewal of skeletal muscle satellite cells. Molecular and Cellular Biology, 32(12), 2300-11. https://doi.org/10.1128/MCB.06753-11
Wen Y, et al. Constitutive Notch Activation Upregulates Pax7 and Promotes the Self-renewal of Skeletal Muscle Satellite Cells. Mol Cell Biol. 2012;32(12):2300-11. PubMed PMID: 22493066.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Constitutive Notch activation upregulates Pax7 and promotes the self-renewal of skeletal muscle satellite cells. AU - Wen,Yefei, AU - Bi,Pengpeng, AU - Liu,Weiyi, AU - Asakura,Atsushi, AU - Keller,Charles, AU - Kuang,Shihuan, Y1 - 2012/04/09/ PY - 2012/4/12/entrez PY - 2012/4/12/pubmed PY - 2013/2/22/medline SP - 2300 EP - 11 JF - Molecular and cellular biology JO - Mol Cell Biol VL - 32 IS - 12 N2 - Notch signaling is a conserved cell fate regulator during development and postnatal tissue regeneration. Using skeletal muscle satellite cells as a model and through myogenic cell lineage-specific NICD(OE) (overexpression of constitutively activated Notch 1 intracellular domain), here we investigate how Notch signaling regulates the cell fate choice of muscle stem cells. We show that in addition to inhibiting MyoD and myogenic differentiation, NICD(OE) upregulates Pax7 and promotes the self-renewal of satellite cell-derived primary myoblasts in culture. Using MyoD(-/-) myoblasts, we further show that NICD(OE) upregulates Pax7 independently of MyoD inhibition. In striking contrast to previous observations, NICD(OE) also inhibits S-phase entry and Ki67 expression and thus reduces the proliferation of primary myoblasts. Overexpression of canonical Notch target genes mimics the inhibitory effects of NICD(OE) on MyoD and Ki67 but not the stimulatory effect on Pax7. Instead, NICD regulates Pax7 through interaction with RBP-Jκ, which binds to two consensus sites upstream of the Pax7 gene. Importantly, satellite cell-specific NICD(OE) results in impaired regeneration of skeletal muscles along with increased Pax7(+) mononuclear cells. Our results establish a role of Notch signaling in actively promoting the self-renewal of muscle stem cells through direct regulation of Pax7. SN - 1098-5549 UR - https://www.unboundmedicine.com/medline/citation/22493066/Constitutive_Notch_activation_upregulates_Pax7_and_promotes_the_self_renewal_of_skeletal_muscle_satellite_cells_ L2 - http://mcb.asm.org/cgi/pmidlookup?view=long&pmid=22493066 DB - PRIME DP - Unbound Medicine ER -