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Control of the Mesenchymal-Derived Cell Phenotype by Ski and Meox2: A Putative Mechanism for Postdevelopmental Phenoconversion

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Molecular Defects in Cardiovascular Disease

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Abstract

The developing mesenchyme gives rise to a diverse host of important cell types, including fibroblasts, endothelial and smooth muscle cells. In postnatal tissues, stromal cells continue to differentiate into subtypes with specific functions, e.g., fibroblasts to myofibroblasts, but the molecular signals that govern their phenoconversion are incompletely understood. Herein, we provide a review of the function of c-Ski (Ski) and Meox2 transcription factors and provide a rationale to support our suggestion that these factors trigger the phenoconversion of “undifferentiated” parenchymal and stromal cells to variants with novel function. As phenoconversion events underlie both normal organ function and the pathogenesis of disease including cardiac fibrosis, we have developed a novel hypothesis to facilitate a clearer understanding of their underlying mechanisms.

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Acknowledgments

This work was supported by a Heart and Stroke Foundation of Manitoba Grant-in-Aid (I.M.C.D.), the Canadian Institutes of Health Research (I.M.C.D. and J.T.W.), and the St. Boniface Hospital Research Foundation (I.M.C.D. and D.H.F.). A.J.H. holds a Canada Research Chair in Airway Cell and Molecular Biology. D.S. is supported by a CIHR fellowship and a CIHR/HSFC IMPACT strategic training program grant in pulmonary and cardiovascular research. R.H.C. is supported by a CIHR-RPP graduate scholarship. S.O. and J.M.D. are supported by an ICS studentship.

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Authors and Affiliations

  1. Department of Physiology, University of Manitoba and the Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, Winnipeg, MB, Canada

    Ryan H. Cunnington, Sarah O’Connor & Ian M. C. Dixon

  2. Department of Biochemistry and Medical Genetics, University of Manitoba and the Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, Winnipeg, MB, Canada

    Josette M. Douville & Jeffrey T. Wigle

  3. Department of Surgery, Section of Cardiac Surgery, University of Manitoba, Winnipeg, MB, Canada

    Darren H. Freed

  4. Department of Physiology, University of Manitoba, Winnipeg, MB, Canada

    Darren H. Freed, Shivika Gupta & Sunil G. Rattan

  5. The Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, Winnipeg, MB, Canada

    Darren H. Freed

  6. Departments of Internal Medicine and Physiology, University of Manitoba, Winnipeg, MB, Canada

    Dedmer Schaafsma & Andrew J. Halayko

  7. The Biology of Breathing Group, Manitoba Institute of Child Health, Winnipeg, MB, Canada

    Dedmer Schaafsma & Andrew J. Halayko

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  1. Ryan H. Cunnington
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  10. Ian M. C. Dixon
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Correspondence to Ian M. C. Dixon .

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  1. St. Boniface General Hospital, Research Centre, Institute of Cardiovascular Sciences, Tache Avenue 351, Winnipeg, R2H 2A6, Manitoba, Canada

    Naranjan S. Dhalla

  2. Jikei University School of Medicine, Shibuya-ku, Ebisu 3-31-6, Tokyo, 150-0013, Japan

    Makoto Nagano

  3. Czech Republic, Institute of Physiology, Academy of Sciences of the, Videnska 1083, Prague, 142 20, Czech Republic

    Bohuslav Ostadal

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Cunnington, R.H. et al. (2011). Control of the Mesenchymal-Derived Cell Phenotype by Ski and Meox2: A Putative Mechanism for Postdevelopmental Phenoconversion. In: Dhalla, N., Nagano, M., Ostadal, B. (eds) Molecular Defects in Cardiovascular Disease. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-7130-2_3

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