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MyoD helps stem cells proliferate in response to muscle injury

Date:
January 11, 2010
Source:
Rockefeller University Press
Summary:
The master regulator of muscle differentiation, MyoD, functions early in myogenesis to help stem cells proliferate in response to muscle injury, according to researchers.
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Activated muscle stem cells express MyoD (red) and Cdc6 (green) as they begin to proliferate.
Credit: Zhang, K., et al. 2010. J. Cell Biol. doi:10.1083/jcb.200904144.

The master regulator of muscle differentiation, MyoD, functions early in myogenesis to help stem cells proliferate in response to muscle injury, according to researchers at Case Western Reserve University.

The study appears online Jan. 4 in the Journal of Cell Biology.

MyoD is a transcription factor that activates muscle-specific genes as myoblast precursors differentiate and fuse to form mature muscle fibers. But MyoD is also expressed at an earlier stage of myogenesis when quiescent stem cells rapidly expand in number to generate the myoblasts needed to repair tissue damage. The transcription factor's function in this proliferative phase is unknown.

The team found that MyoD bound to the promoter of CDC6, a gene that initiates DNA replication, suggesting that MyoD might activate Cdc6 expression in muscle stem cells to promote their reentry into the cell cycle and rapid proliferation. Indeed, Cdc6 was expressed shortly after MyoD in stimulated muscle progenitors, and knocking down MyoD reduced Cdc6 production and slowed cells' entry into S phase. MyoD works in conjunction with transcription factors from the E2F family. E2F3a activated the CDC6 promoter with MyoD, but was replaced by the repressive family member E2F4 as myoblasts began to differentiate.

Senior author Nikki Harter now wants to investigate how the transcription factors cooperate to control Cdc6 expres-sion -- initial results suggest that MyoD recruits E2F3a to the promoter region. The researchers also propose that a related protein, Myf5, might control Cdc6 transcription in MyoD's absence, acting as a backup mechanism to ensure that muscle stem cells expand to repair tissue damage.


Story Source:

The above post is reprinted from materials provided by Rockefeller University Press. Note: Materials may be edited for content and length.


Journal Reference:

  1. Keman Zhang, Jingfeng Sha, and Marian L. Harter. Activation of Cdc6 by MyoD is associated with the expansion of quiescent myogenic satellite cells. The Journal of Cell Biology, 2010; DOI: 10.1083/jcb.200904144

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Rockefeller University Press. "MyoD helps stem cells proliferate in response to muscle injury." ScienceDaily. ScienceDaily, 11 January 2010. <www.sciencedaily.com/releases/2010/01/100104091130.htm>.
Rockefeller University Press. (2010, January 11). MyoD helps stem cells proliferate in response to muscle injury. ScienceDaily. Retrieved July 6, 2015 from www.sciencedaily.com/releases/2010/01/100104091130.htm
Rockefeller University Press. "MyoD helps stem cells proliferate in response to muscle injury." ScienceDaily. www.sciencedaily.com/releases/2010/01/100104091130.htm (accessed July 6, 2015).

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