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Satellite cell heterogeneity with respect to expression of MyoD, myogenin, Dlk1 and c-Met in human skeletal muscle: application to a cohort of power lifters and sedentary men
Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy. Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
2010 (English)In: Histochemistry and Cell Biology, ISSN 0948-6143, E-ISSN 1432-119X, Vol. 134, no 4, 371-385 p.Article in journal (Refereed) Published
Abstract [en]

Human satellite cells (SCs) are heterogeneous with respect to markers for their identification in the niche between the muscle fibre plasma membrane and its basal lamina. We have previously shown that, in biopsies from highly competitive power lifters, power lifters with long-term use of anabolic steroids and a population of healthy sedentary men, antibodies against the neuronal cell adhesion molecule (NCAM) and the paired box transcription factor Pax7 together label 94% of the SCs, NCAM alone labels 4% and Pax7 alone labels 1%. In the present study, we have further studied these biopsies with four markers related to SC activation and differentiation. Our study unequivocally shows that staining for MyoD and myogenin are present in nuclei of SCs and of myoblasts and myotubes in areas of muscle fibre regeneration. Staining for c-Met was observed in a proportion of Pax7+ SCs. However, widespread labelling of the sarcolemma precluded the quantification of c-Met+/Pax7+ SCs and the use of c-Met as a reliable SC marker. Pax7+ SCs labelled by anti-Delta like1 (Dlk1) were present in all samples but in variable proportions, whereas muscle progenitor cells related to repair were Dlk1⁻. Staining for Dlk1 was also observed in Pax7⁻ interstitial cells and in the cytoplasm of some small muscle fibres. Interestingly, the proportion of Dlk1+/Pax7+ SCs was significantly different between the groups of power lifters. Thus, our study confirms that human SCs show marked heterogeneity and this is discussed in terms of SC activation, myonuclei turnover, muscle fibre growth and muscle fibre damage and repair.

Place, publisher, year, edition, pages
2010. Vol. 134, no 4, 371-385 p.
Keyword [en]
Skeletal muscle satellite cells, Myogenic regulatory factors, Pax7, Dlk1/FA1, Strength training, Anabolic steroids
URN: urn:nbn:se:umu:diva-42310DOI: 10.1007/s00418-010-0743-5ISI: 000282974600008PubMedID: 20878332OAI: diva2:409102
Available from: 2011-04-07 Created: 2011-04-07 Last updated: 2011-04-13Bibliographically approved
In thesis
1. Satellite cells in human skeletal muscle: molecular identification quantification and function
Open this publication in new window or tab >>Satellite cells in human skeletal muscle: molecular identification quantification and function
2009 (English)Doctoral thesis, comprehensive summary (Other academic)
Alternative title[sv]
Satellitceller i human skelettmuskulatur : molekylär identifiering, kvantifiering och funktion
Abstract [en]

Skeletal muscle satellite cells located between the plasma membrane and the basal lamina of muscle fibres, could for many years, only be studied in situ by electron microscopy. The introduction of immunohistochemistry and the discovery of molecular markers of satellite cells then made them accessible for light microscopic studies and a wealth of information is today available. Satellite cells are myogenic stem cells that can be activated from a quiescent state to proliferate for self-renewal or differentiate into myogenic cells. The satellite cells are involved in muscle growth during fetal and postnatal development and play a key role in repair and regeneration of damaged muscle fibres. The satellite cells are also essential for muscle fibre hypertrophy and maintenance of muscle mass in the adult. When the present thesis was initiated, studies on satellite cells in human skeletal muscle relied on the neuronal cell adhesion molecule (NCAM) as a marker for satellite cell identification. The results from different studies varied markedly. Therefore the aims of the present thesis were i) to develop a highly reliable method using light microscopy for satellite cell identification and quantification in biopsies of human skeletal muscle in normal and pathological conditions. A molecular marker for the myofibre basal lamina or plasma membrane to enhance the reliability of myonuclei and satellite cell identification were to be included. Furthermore unbiased morphometric methods should be used in the quantification process. ii) to evaluate which molecular markers which had been described for satellite cell and stem cell identification in different cell states (quiescence, activated or differentiated) are the most useful for studies on human skeletal muscle. iii) to further explore the function and heterogeneity of satellite cells with respect to different markers in human skeletal muscle by studying the effects of strength-training, intake of anabolic substances and pathological conditions.

A new immunofluorescence method was developed where in the same tissue section, two satellite cell markers, the basal lamina and nuclei were monitored. From the evaluation of different markers it was found that both NCAM and Pax7 identified the majority of satellite cells but that both markers were needed for reliable identification. The members of the myogenic regulatory family were evaluated and by using the new method MyoD and myogenin were found to be useful markers to identify activated and differentiated satellite cells. Upon re-examination of biopsies from power-lifters, power-lifters using anabolic substances and untrained subjects it was observed that the new results on satellite cell frequency were significantly different from those obtained when using staining for NCAM and nuclei alone. In addition three subtypes of satellite cells (94.4% NCAM+/Pax7+, 4.2% NCAM+/Pax7 and 1.4% NCAM/Pax7+) were observed. Thus the multiple marker method gave more information about satellite cells heterogeneity in human muscle and we propose that this is more reliable than previous methods. Low numbers of MyoD or myogenin stained satellite cells were observed in both untrained and strength trained subjects. Other markers such as DLK1/FA1, a member of the EGF-like family and c-Met, the receptor for hepatocyte growth factor showed that satellite cell heterogeneity in human muscle is far greater than previously shown. Furthermore, new evidence is presented for so called fibre splitting observed in hypertrophic muscle fibres to be due to defect regeneration of partially damaged fibres.

Place, publisher, year, edition, pages
Umeå: Umeå University, 2009. 56 p.
Umeå University medical dissertations, ISSN 0346-6612 ; 1313
satellite cell markers, NCAM, Pax7, MyoD, myogenin, DLK1/FA1, c-Met, human skeletal muscle, immunohistochemistry, muscle growth, muscle hypertrophy
National Category
Cell and Molecular Biology
Research subject
Human Anatomy
urn:nbn:se:umu:diva-29817 (URN)978-91-7264-900-2 (ISBN)
Public defence
2009-12-18, Biologihuset, sal BiA201, Umeå Universitet, Umeå, 09:00 (Swedish)
Available from: 2009-12-01 Created: 2009-11-24 Last updated: 2011-04-07Bibliographically approved

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