Sca-1 negatively regulates proliferation and differentiation of muscle cells

Department of Cell Biology, Erasmus Universiteit Rotterdam, Rotterdam, South Holland, Netherlands
Developmental Biology (Impact Factor: 3.55). 08/2005; 283(1):240-52. DOI: 10.1016/j.ydbio.2005.04.016
Source: PubMed


Satellite cells are tissue-specific stem cells critical for skeletal muscle growth and regeneration. Upon exposure to appropriate stimuli, satellite cells produce progeny myoblasts. Heterogeneity within a population of myoblasts ensures that a subset of myoblasts readily differentiate to form myotubes, whereas other myoblasts remain undifferentiated and thus available for future muscle growth. The mechanisms that contribute to this heterogeneity in myoblasts are largely unknown. We show that satellite cells are Sca-1(neg) but give rise to myoblasts that are heterogeneous for sca-1 expression. The majority of myoblasts are sca-1(neg), rapidly divide, and are capable of undergoing myogenic differentiation to form myotubes. In contrast, a minority population is sca-1(pos), divides slower, and does not readily form myotubes. Sca-1 expression is not static but rather dynamically modulated by the microenvironment. Gain-of-function and loss-of-function experiments demonstrate that sca-1 has a functional role in regulating proliferation and differentiation of myoblasts. Myofiber size of sca-1 null muscles is altered in an age-dependent manner, with increased size observed in younger mice and decreased size in older mice. These studies reveal a novel system that reversibly modulates the myogenic behavior of myoblasts. These studies provide evidence that, rather than being a fixed property, myoblast heterogeneity can be modulated by the microenvironment.

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Available from: Grace K Pavlath, Feb 15, 2014
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    • "However, the in vitro study of stem cells often does not consider a niche environment. Rather, attempts to study stem cells have predominantly focused on the isolation of purified subsets of cells with specific markers or functions12345678910. Yet, several reports suggest that a population level exists for various stem cell types including hematopoietic stem cells (HSCs), mesenchymal stem cells (MSCs)111213and muscle stem cells14151617181920. In support of this, several groups have shown that an individual cell from a stem cell population can re-establish the heterogeneous parent population2122232425. "
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    • "Plasmids PM4 (which encodes a retroviral vector containing the cDNA for Ly6a/Sca-1 as well as the eGFP and zeocin resistance gene cDNAs) and pTJ66 (the control plasmid which encodes a retroviral vector that contains eGFP and zeocin resistance cDNAs) were gifts of Dr. G. K. Pavlath of Emory University [17]. Retrovirus was produced by lipofectamine facilitated transient transfection of helper-free retroviral vector producer Phoenix cell lines with plasmids PM4 or pTJ66. "
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    • "We previously reported that inhibition of Sca-1 expression by antisense or Sca-1 interference with blocking antibodies stimulated myoblast proliferation and delayed myoblast fusion in vitro19. Subsequently, others observed sustained proliferation in Sca-1-/- myoblasts cultured ex vivo 20 . Using a myonecrotic injury model in Sca-1-/- and Sca-1+/+ mice, we then showed that Sca-1 regulates the tempo of muscle repair by controlling the balance between proliferation and differentiation of activated myoblasts 21 . "
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