NDLI: Isolation and characterization of embryonic stem cell-derived cardiac Purkinje cells.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Maass, Karen Shekhar, Akshay Lu, Jia Kang, Guoxin See, Fiona Kim, Eugene E. Delgado, Camila Shen, Steven Cohen, Lisa Fishman, Glenn I.
Description	Country affiliation: United States Author Affiliation: Maass K ( Leon H. Charney Division of Cardiology, New York University School of Medicine, New York, New York, USA.)
Abstract	The cardiac Purkinje fiber network is composed of highly specialized cardiomyocytes responsible for the synchronous excitation and contraction of the ventricles. Computational modeling, experimental animal studies, and intracardiac electrical recordings from patients with heritable and acquired forms of heart disease suggest that Purkinje cells (PCs) may also serve as critical triggers of life-threatening arrhythmias. Nonetheless, owing to the difficulty in isolating and studying this rare population of cells, the precise role of PC in arrhythmogenesis and the underlying molecular mechanisms responsible for their proarrhythmic behavior are not fully characterized. Conceptually, a stem cell-based model system might facilitate studies of PC-dependent arrhythmia mechanisms and serve as a platform to test novel therapeutics. Here, we describe the generation of murine embryonic stem cells (ESC) harboring pan-cardiomyocyte and PC-specific reporter genes. We demonstrate that the dual reporter gene strategy may be used to identify and isolate the rare ESC-derived PC (ESC-PC) from a mixed population of cardiogenic cells. ESC-PC display transcriptional signatures and functional properties, including action potentials, intracellular calcium cycling, and chronotropic behavior comparable to endogenous PC. Our results suggest that stem-cell derived PC are a feasible new platform for studies of developmental biology, disease pathogenesis, and screening for novel antiarrhythmic therapies.
File Format	HTM / HTML
ISSN	10665099
e-ISSN	15494918
DOI	10.1002/stem.1921
Journal	STEM CELLS
Issue Number	4
Volume Number	33
Language	English
Publisher	Wiley
Publisher Date	2015-04-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Discipline Cell Biology Discipline Embryology Cell Culture Techniques Embryonic Stem Cells Physiology Myocytes, Cardiac Purkinje Fibers Cytology Animals Blastocyst Cells, Cultured Mice Mice, Inbred C57bl Mice, Transgenic Research Support, N.i.h., Extramural Research Support, Non-u.s. Gov't
Content Type	Text
Resource Type	Article
Subject	Cell Biology Developmental Biology Medicine Molecular Medicine

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