title: Live cell imaging reveals marked variability in myoblast proliferation and fate.
abstract: BACKGROUND
  During the process of muscle regeneration, activated stem cells termed satellite cells proliferate, and then differentiate to form new myofibers that restore the injured area. Yet not all satellite cells contribute to muscle repair. Some continue to proliferate, others die, and others become quiescent and are available for regeneration following subsequent injury. The mechanisms that regulate the adoption of different cell fates in a muscle cell precursor population remain unclear.
  
  
  METHODS
  We have used live cell imaging and lineage tracing to study cell fate in the C2 myoblast line.
  
  
  RESULTS
  Analyzing the behavior of individual myoblasts revealed marked variability in both cell cycle duration and viability, but similarities between cells derived from the same parental lineage. As a consequence, lineage sizes and outcomes differed dramatically, and individual lineages made uneven contributions toward the terminally differentiated population. Thus, the cohort of myoblasts undergoing differentiation at the end of an experiment differed dramatically from the lineages present at the beginning. Treatment with IGF-I increased myoblast number by maintaining viability and by stimulating a fraction of cells to complete one additional cell cycle in differentiation medium, and as a consequence reduced the variability of the terminal population compared with controls.
  
  
  CONCLUSIONS
  Our results reveal that heterogeneity of responses to external cues is an intrinsic property of cultured myoblasts that may be explained in part by parental lineage, and demonstrate the power of live cell imaging for understanding how muscle differentiation is regulated.
authors: Department of Biochemistry and Molecular Biology, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, OR, 97239-3098, USA. rotweinp@ohsu.edu.
authors: Sean M
authors: SM
authors: Gross
authors: Peter
authors: P
authors: Rotwein
references: J Cell Sci. 1996 Mar;109 ( Pt 3):551-60
references: 8907701
references: Nat Cell Biol. 2006 Jul;8(7):677-87
references: 16799552
references: Exp Cell Res. 1986 Nov;167(1):63-74
references: 3758210
references: Nature. 1977 Dec 22-29;270(5639):725-7
references: 563524
references: J Cell Biol. 2004 Aug 2;166(3):347-57
references: 15277541
references: Int J Biochem Cell Biol. 1999 Dec;31(12):1373-90
references: 10641792
references: Mol Cell Biol. 2012 Jan;32(2):490-500
references: 22064480
references: Physiol Rev. 2004 Jan;84(1):209-38
references: 14715915
references: Nature. 2008 Nov 27;456(7221):502-6
references: 18806774
references: J Cell Sci. 1998 Mar;111 ( Pt 6):769-79
references: 9472005
references: Nature. 2010 Jul 8;466(7303):267-71
references: 20581820
references: Cell. 2011 Mar 18;144(6):926-39
references: 21414484
references: Cell. 2007 Jun 1;129(5):999-1010
references: 17540178
references: J Biol Chem. 1997 Mar 7;272(10):6653-62
references: 9045696
references: J Cell Biochem. 2009 Oct 1;108(2):343-52
references: 19626666
references: Mol Cell Biol. 1999 Jul;19(7):5073-82
references: 10373556
references: Trends Cell Biol. 2009 Jun;19(6):286-94
references: 19394225
references: Physiol Rev. 2013 Jan;93(1):23-67
references: 23303905
references: Curr Opin Cell Biol. 1994 Dec;6(6):788-94
references: 7880524
references: Cell Stem Cell. 2008 Jan 10;2(1):22-31
references: 18371418
references: Stem Cells. 2009 Oct;27(10):2527-38
references: 19609936
references: Science. 1996 Jul 19;273(5273):359-61
references: 8662523
references: Mol Cell Biol. 2010 Feb;30(4):1018-27
references: 19995912
references: Semin Cell Dev Biol. 2010 Oct;21(8):845-54
references: 20849971
references: Curr Opin Genet Dev. 2010 Dec;20(6):677-83
references: 20846851
references: Am J Physiol Cell Physiol. 2012 Dec 15;303(12):C1292-300
references: 23076793
references: Nature. 2009 May 21;459(7245):428-32
references: 19363473
references: Nature. 2003 Apr 10;422(6932):633-7
references: 12687005
references: Nature. 2005 Sep 29;437(7059):699-706
references: 16170311
references: Science. 1995 Feb 17;267(5200):1022-4
references: 7863328
references: Mol Cell Biol. 2000 Dec;20(23):8983-95
references: 11073997
references: Skelet Muscle. 2011 Feb 02;1(1):7
references: 21798086
references: Methods Mol Biol. 2009;559:313-32
references: 19609766
references: J Intern Med. 2009 Oct;266(4):372-89
references: 19765181
references: Mol Cell Biol. 2000 May;20(9):3256-65
references: 10757809
references: Stem Cell Res Ther. 2010 Aug 26;1(3):27
references: 20804582
references: J Biol Chem. 1996 May 10;271(19):11330-8
references: 8626686
references: Mol Biol Cell. 2004 Feb;15(2):497-505
references: 14595115
references: Genome Biol. 2006;7(10):R100
references: 17076895
references: Science. 1995 Feb 17;267(5200):1018-21
references: 7863327