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Myocardial Notch Signaling Reprograms Cardiomyoctes to a Conduction‐Like Phenotype
Author(s) -
Rentschler Stacey,
Yen Alberta,
Lu Jia,
Petrenko Nataliya,
Patel Vickas V,
Fishman Glenn I,
Epstein Jonathan A
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.209.4
Subject(s) - notch signaling pathway , microbiology and biotechnology , phenotype , cell fate determination , biology , ectopic expression , stem cell , progenitor cell , neuroscience , signal transduction , transcription factor , gene , genetics
Notch signaling has previously been shown to play an essential role in regulating cell fate decisions in many systems. We hypothesized that Notch may be involved in directing the progressive lineage restriction of cardiomyocytes into specialized conduction cells. In murine hearts where Notch signaling is activated within the myocardium from early development onwards, Notch promotes a conduction‐like phenotype as evidenced by ectopic expression of conduction system‐specific genes, as well as cell autonomous changes in cellular electrophysiology. Activation of Notch in newborn ventricular cardiomyocytes from Contactin2‐EGFP transgenic mice, which specifically labels conduction cells, demonstrates Notch‐induced changes in “chamber” ventricular cardiomyocytes consistent with a phenotypic switch to Purkinje‐like cells, including transcriptional changes, action potential prolongation and hyperpolarization of the resting membrane potential. Taken together, this suggests that Notch can instruct the differentiation of cardiac progenitors into specialized conduction‐like cells and that this plasticity remains in late‐stage cardiomyocytes, which has potential implications for engineering of specialized cardiovascular tissues. Grant Funding Source : Career Award for Medical Scientists Burroughs Wellcome Fund and K08 HL107449‐01 to SR, U01 HL100405‐1 to JAE