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Myostatin signals through Pax7 to regulate satellite cell self-renewal.
Exp Cell Res. 2008 Jan 15; 314(2):317-29.EC

Abstract

Myostatin, a Transforming Growth Factor-beta (TGF-beta) super-family member, has previously been shown to negatively regulate satellite cell activation and self-renewal. However, to date the mechanism behind Myostatin function in satellite cell biology is not known. Here we show that Myostatin signals via a Pax7-dependent mechanism to regulate satellite cell self-renewal. While excess Myostatin inhibited Pax7 expression via ERK1/2 signaling, an increase in Pax7 expression was observed following both genetic inactivation and functional antagonism of Myostatin. As a result, we show that either blocking or inactivating Myostatin enhances the partitioning of the fusion-incompetent self-renewed satellite cell lineage (high Pax7 expression, low MyoD expression) from the pool of actively proliferating myogenic precursor cells. Consistent with this result, over-expression of Pax7 in C2C12 myogenic cells resulted in increased self-renewal through a mechanism which slowed both myogenic proliferation and differentiation. Taken together, these results suggest that increased expression of Pax7 promotes satellite cell self-renewal, and furthermore Myostatin may control the process of satellite cell self-renewal through regulation of Pax7. Thus we speculate that, in addition to the intrinsic factors (such as Pax7), extrinsic factors both positive and negative in nature, will play a major role in determining the stemness of skeletal muscle satellite cells.

Authors+Show Affiliations

AgResearch, Functional Muscle Genomics, Hamilton, New Zealand.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

17949710

Citation

McFarlane, Craig, et al. "Myostatin Signals Through Pax7 to Regulate Satellite Cell Self-renewal." Experimental Cell Research, vol. 314, no. 2, 2008, pp. 317-29.
McFarlane C, Hennebry A, Thomas M, et al. Myostatin signals through Pax7 to regulate satellite cell self-renewal. Exp Cell Res. 2008;314(2):317-29.
McFarlane, C., Hennebry, A., Thomas, M., Plummer, E., Ling, N., Sharma, M., & Kambadur, R. (2008). Myostatin signals through Pax7 to regulate satellite cell self-renewal. Experimental Cell Research, 314(2), 317-29.
McFarlane C, et al. Myostatin Signals Through Pax7 to Regulate Satellite Cell Self-renewal. Exp Cell Res. 2008 Jan 15;314(2):317-29. PubMed PMID: 17949710.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Myostatin signals through Pax7 to regulate satellite cell self-renewal. AU - McFarlane,Craig, AU - Hennebry,Alex, AU - Thomas,Mark, AU - Plummer,Erin, AU - Ling,Nicholas, AU - Sharma,Mridula, AU - Kambadur,Ravi, Y1 - 2007/09/22/ PY - 2007/06/20/received PY - 2007/09/12/revised PY - 2007/09/15/accepted PY - 2007/10/24/pubmed PY - 2008/3/6/medline PY - 2007/10/24/entrez SP - 317 EP - 29 JF - Experimental cell research JO - Exp Cell Res VL - 314 IS - 2 N2 - Myostatin, a Transforming Growth Factor-beta (TGF-beta) super-family member, has previously been shown to negatively regulate satellite cell activation and self-renewal. However, to date the mechanism behind Myostatin function in satellite cell biology is not known. Here we show that Myostatin signals via a Pax7-dependent mechanism to regulate satellite cell self-renewal. While excess Myostatin inhibited Pax7 expression via ERK1/2 signaling, an increase in Pax7 expression was observed following both genetic inactivation and functional antagonism of Myostatin. As a result, we show that either blocking or inactivating Myostatin enhances the partitioning of the fusion-incompetent self-renewed satellite cell lineage (high Pax7 expression, low MyoD expression) from the pool of actively proliferating myogenic precursor cells. Consistent with this result, over-expression of Pax7 in C2C12 myogenic cells resulted in increased self-renewal through a mechanism which slowed both myogenic proliferation and differentiation. Taken together, these results suggest that increased expression of Pax7 promotes satellite cell self-renewal, and furthermore Myostatin may control the process of satellite cell self-renewal through regulation of Pax7. Thus we speculate that, in addition to the intrinsic factors (such as Pax7), extrinsic factors both positive and negative in nature, will play a major role in determining the stemness of skeletal muscle satellite cells. SN - 0014-4827 UR - https://www.unboundmedicine.com/medline/citation/17949710/Myostatin_signals_through_Pax7_to_regulate_satellite_cell_self_renewal_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-4827(07)00443-0 DB - PRIME DP - Unbound Medicine ER -