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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 404-410 |
| Number of pages | 7 |
| Journal | European Journal of Human Genetics |
| Volume | 20 |
| Issue number | 4 |
| DOIs | |
| State | Published - Apr 2012 |
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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 Rae; 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: Contribution to journal › Article
}
TY - JOUR
T1 - A unique library of myogenic cells from facioscapulohumeral muscular dystrophy subjects and unaffected relatives
T2 - Family, disease and cell function
AU - Homma, Sachiko
AU - Chen, Jennifer C J
AU - Rahimov, Fedik
AU - Beermann, Mary Lou
AU - Hanger, Kendal
AU - Bibat, Genila M
AU - Wagner, Kathryn Rae
AU - Kunkel, Louis M.
AU - Emerson, Charles P.
AU - Miller, Jeffrey Boone
PY - 2012/4
Y1 - 2012/4
N2 - 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.
AB - 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.
KW - facioscapulohumeral muscular dystrophy
KW - family influence
KW - gene expression
KW - myogenesis
KW - stress response
UR - http://www.scopus.com/inward/record.url?scp=84858334928&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84858334928&partnerID=8YFLogxK
U2 - 10.1038/ejhg.2011.213
DO - 10.1038/ejhg.2011.213
M3 - Article
C2 - 22108603
AN - SCOPUS:84858334928
VL - 20
SP - 404
EP - 410
JO - European Journal of Human Genetics
JF - European Journal of Human Genetics
SN - 1018-4813
IS - 4
ER -