Efficient Generation of Cardiac Purkinje Cells from ESCs by Activating cAMP Signaling.
Stem Cell Reports
; 4(6): 1089-102, 2015 Jun 09.
Article
en En
| MEDLINE
| ID: mdl-26028533
ABSTRACT
Dysfunction of the specialized cardiac conduction system (CCS) is associated with life-threatening arrhythmias. Strategies to derive CCS cells, including rare Purkinje cells (PCs), would facilitate models for mechanistic studies and drug discovery and also provide new cellular materials for regenerative therapies. A high-throughput chemical screen using CCSlacz and Contactin2egfp (Cntn2egfp) reporter embryonic stem cell (ESC) lines was used to discover a small molecule, sodium nitroprusside (SN), that efficiently promotes the generation of cardiac cells that express gene profiles and generate action potentials of PC-like cells. Imaging and mechanistic studies suggest that SN promotes the generation of PCs from cardiac progenitors initially expressing cardiac myosin heavy chain and that it does so by activating cyclic AMP signaling. These findings provide a strategy to derive scalable PCs, along with insight into the ontogeny of CCS development.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Células de Purkinje
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AMP Cíclico
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Miocitos Cardíacos
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Células Madre Embrionarias
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Año:
2015
Tipo del documento:
Article