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: 3.64). 08/2005; 283(1):240-52. DOI: 10.1016/j.ydbio.2005.04.016
Source: PubMed

ABSTRACT 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.


Available from: Grace K Pavlath, Feb 15, 2014
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: FALC cells are natural helper cells producing Th2-type cytokines, which express c-kit, Sca-1, IL7R and CD45 in mouse and human. These cells are involved in allergic responses and contribute to the inflammatory reactions of adipose tissue; however, a lack of information prevails about the presence of these cells in other species. The aim of the study was to identify and characterise FALC cells in the common carp (Cyprinus carpio) using immunohistochemistry and molecular biology techniques as well as to explore their relationships with their microenvironment. Histological description of the FALC was performed using H&E and polyclonal antibodies were used against cell-surface markers such as c-kit, Sca-1 and CD45. Furthermore, gene expression of c-kit, Sca-1 and IL7R was assessed. C. carpio FALC cells express the same surface markers reported in FALC of the mouse at both the pre- and post-transcriptional level. By exposure to the soluble fraction of helminths, FALC cells produce abundant Th2 cytokines (IL-5, IL-6 and IL-13) but do not synthesise IL-1α. Additionally, FALC cells probably participate in vascular remodelling of the intestine vessels, inducing tumours because a malignant haemangiosarcoma in the peritoneal cavity was found. In this tumour, abundant FALC with their characteristic cell-surface markers were detected. The findings of this study suggest the involvement of some proto-oncogenes such as c-kit and Sca-1, and the deregulation of Src kinases modulated by CD45 present in Cyprinus carpio FALC with the ontogeny of peritoneal haemangiosarcoma in this fish species. Copyright © 2015. Published by Elsevier Ltd.
    Fish &amp Shellfish Immunology 03/2015; 44(2). DOI:10.1016/j.fsi.2015.03.019 · 3.03 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Setdb1, an H3-K9 specific histone methyltransferase, is associated with transcriptional silencing of euchromatic genes through chromatin modification. Functions of Setdb1 during development have been extensively studied in embryonic and mesenchymal stem cells as well as neurogenic progenitor cells. But the role of Sedtdb1 in myogenic differentiation remains unknown. In this study, we report that Setdb1 is required for myogenic potential of C2C12 myoblast cells through maintaining the expressions of MyoD and muscle-specific genes. We find that reduced Setdb1 expression in C2C12 myoblast cells severely delayed differentiation of C2C12 myoblast cells, whereas exogenous Setdb1 expression had little effect on. Gene expression profiling analysis using oligonucleotide microarray and RNA-Seq technologies demonstrated that depletion of Setdb1 results in downregulation of MyoD as well as the components of muscle fiber in proliferating C2C12 cells. In addition, exogenous expression of MyoD reversed transcriptional repression of MyoD promoter-driven luciferase reporter by Setdb1 shRNA and rescued myogenic differentiation of C2C12 myoblast cells depleted of endogenous Setdb1. Taken together, these results provide new insights into how levels of key myogenic regulators are maintained prior to induction of differentiation.
    Molecules and Cells 02/2015; 38(4). DOI:10.14348/molcells.2015.2291 · 2.24 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Understanding stem cell (SC) population dynamics is essential for developing models that can be used in basic science and medicine, to aid in predicting cells fate. These models can be used as tools e.g. in studying patho-physiological events at the cellular and tissue level, predicting (mal)functions along the developmental course, and personalized regenerative medicine. Using time-lapsed imaging and statistical tools, we show that the dynamics of SC populations involve a heterogeneous structure consisting of multiple sub-population behaviors. Using non-Gaussian statistical approaches, we identify the co-existence of fast and slow dividing subpopulations, and quiescent cells, in stem cells from three species. The mathematical analysis also shows that, instead of developing independently, SCs exhibit a time-dependent fractal behavior as they interact with each other through molecular and tactile signals. These findings suggest that more sophisticated models of SC dynamics should view SC populations as a collective and avoid the simplifying homogeneity assumption by accounting for the presence of more than one dividing sub-population, and their multi-fractal characteristics.
    Scientific Reports 04/2014; 4:4826. DOI:10.1038/srep04826 · 5.08 Impact Factor