A unique library of myogenic cells from facioscapulohumeral muscular dystrophy subjects and unaffected relatives: Family, disease and cell function

Sachiko Homma, Jennifer C J Chen, Fedik Rahimov, Mary Lou Beermann, Kendal Hanger, Genila M. Bibat, Kathryn R. Wagner, Louis M. Kunkel, Charles P. Emerson, Jeffrey Boone Miller

Research output: Research - peer-reviewArticle

Abstract

To explore possible mechanisms of pathology in facioscapulohumeral muscular dystrophy (FSHD), we generated a novel library of myogenic cells composed of paired cultures derived from FSHD subjects and unaffected first-degree relatives. We prepared cells from biopsies of both biceps and deltoid muscles obtained from each of 10 FSHD and 9 unaffected donors. We used this new collection to determine how family background and disease affected patterns of growth and differentiation, expression of a panel of candidate, and muscle-specific genes, and responses to exogenous stressors. We found that FSHD and unaffected cells had, on average, indistinguishable patterns of differentiation, gene expression, and dose-response curves to staurosporine, paraquat, hydrogen peroxide, and glutathione depletion. Differentiated FSHD and unaffected cultures were both more sensitive to glutathione depletion than proliferating cultures, but showed similar responses to paraquat, staurosporine, and peroxide. For stress responses, the sample size was sufficient to detect a 10% change in effect at the observed variability with a power of >99%. In contrast, for each of these properties, we found significant differences among cells from different cohorts, and these differences were independent of disease status, gender, or muscle biopsied. Thus, though none of the properties we examined could be used to reliably distinguish between FSHD and unaffected cells, family of origin was an important contributor to gene-expression patterns and stressor responses in cultures of both FSHD and unaffected myogenic cells.

LanguageEnglish (US)
Pages404-410
Number of pages7
JournalEuropean Journal of Human Genetics
Volume20
Issue number4
DOIs
StatePublished - Apr 2012

Fingerprint

Facioscapulohumeral Muscular Dystrophy
Paraquat
Staurosporine
Glutathione
Gene Expression
Muscles
Deltoid Muscle
Peroxides
Sample Size
Hydrogen Peroxide
Pathology
Biopsy
Growth
Genes

Keywords

  • facioscapulohumeral muscular dystrophy
  • family influence
  • gene expression
  • myogenesis
  • stress response

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

A unique library of myogenic cells from facioscapulohumeral muscular dystrophy subjects and unaffected relatives : Family, disease and cell function. / Homma, Sachiko; Chen, Jennifer C J; Rahimov, Fedik; Beermann, Mary Lou; Hanger, Kendal; Bibat, Genila M.; Wagner, Kathryn R.; Kunkel, Louis M.; Emerson, Charles P.; Miller, Jeffrey Boone.

In: European Journal of Human Genetics, Vol. 20, No. 4, 04.2012, p. 404-410.

Research output: Research - peer-reviewArticle

Homma, Sachiko ; Chen, Jennifer C J ; Rahimov, Fedik ; Beermann, Mary Lou ; Hanger, Kendal ; Bibat, Genila M. ; Wagner, Kathryn R. ; Kunkel, Louis M. ; Emerson, Charles P. ; Miller, Jeffrey Boone. / A unique library of myogenic cells from facioscapulohumeral muscular dystrophy subjects and unaffected relatives : Family, disease and cell function. In: European Journal of Human Genetics. 2012 ; Vol. 20, No. 4. pp. 404-410
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