Academic Journal
Contractile Defect Caused by Mutation in MYBPC3 Revealed under Conditions Optimized for Human PSC-Cardiomyocyte Function
| العنوان: | Contractile Defect Caused by Mutation in MYBPC3 Revealed under Conditions Optimized for Human PSC-Cardiomyocyte Function |
|---|---|
| المؤلفون: | Birket, M.J. (Matthew J.), Ribeiro, M.C. (Marcelo C.), Kosmidis, G. (Georgios), Ward, D. (Dorien), Leitoguinho, A.R. (Ana Rita), van de Pol, V. (Vera), Dambrot, C. (Cheryl), Devalla, H.D. (Harsha D.), Davis, R.P. (Richard P.), Mastroberardino, P.G. (Pier), Atsma, D.E. (Douwe), Passier, R. (Robert), Mummery, C.L. (Christine) |
| المصدر: | Cell Reports vol. 13 no. 4, pp. 733-745 |
| سنة النشر: | 2015 |
| المجموعة: | RePub - Publications from Erasmus University, Rotterdam |
| الوصف: | Maximizing baseline function of human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) is essential for their effective application in models of cardiac toxicity and disease. Here, we aimed to identify factors that would promote an adequate level of function to permit robust single-cell contractility measurements in a human induced pluripotent stem cell (hiPSC) model of hypertrophic cardiomyopathy (HCM). A simple screen revealed the collaborative effects of thyroid hormone, IGF-1 and the glucocorticoid analog dexamethasone on the electrophysiology, bioenergetics, and contractile force generation of hPSC-CMs. In this optimized condition, hiPSC-CMs with mutations in MYBPC3, a gene encoding myosin-binding protein C, which, when mutated, causes HCM, showed significantly lower contractile force generation than controls. This was recapitulated by direct knockdown of MYBPC3 in control hPSC-CMs, supporting a mechanism of haploinsufficiency. Modeling this disease in vitro using human cells is an important step toward identifying therapeutic interventions for HCM. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| Relation: | http://repub.eur.nl/pub/81168; urn:hdl:1765/81168 |
| DOI: | 10.1016/j.celrep.2015.09.025 |
| الاتاحة: | http://repub.eur.nl/pub/81168 https://doi.org/10.1016/j.celrep.2015.09.025 |
| Rights: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.E06224BC |
| قاعدة البيانات: | BASE |
| DOI: | 10.1016/j.celrep.2015.09.025 |
|---|