New Approaches to Biological Pacemakers: Links to Sinoatrial Node Development

Keith, 1907, The form and nature of the muscular connections between the primary divisions of the vertebrate heart, J. Anat. Physiol., 41, 172 Fedorov, 2010, Optical mapping of the isolated coronary-perfused human sinus node, J. Am. Coll. Cardiol., 56, 1386, 10.1016/j.jacc.2010.03.098 Mond, 2011, The 11th world survey of cardiac pacing and implantable cardioverter-defibrillators: calendar year 2009 – a World Society of Arrhythmia's project, Pacing Clin. Electrophysiol., 34, 1013, 10.1111/j.1540-8159.2011.03150.x Bleeker, 1980, Functional and morphological organization of the rabbit sinus node, Circ. Res., 46, 11, 10.1161/01.RES.46.1.11 Mangoni, 2008, Genesis and regulation of the heart automaticity, Physiol. Rev., 88, 919, 10.1152/physrev.00018.2007 Meyers, 2015, Reprogramming the conduction system: Onward toward a biological pacemaker, Trends Cardiovasc. Med. Boink, 2015, The past, present, and future of pacemaker therapies, Trends Cardiovasc. Med., 10.1016/j.tcm.2015.02.005 Li, 2012, Gene- and cell-based bio-artificial pacemaker: what basic and translational lessons have we learned?, Gene Ther., 19, 588, 10.1038/gt.2012.33 Rosen, 2011, The road to biological pacing, Nat. Rev. Cardiol., 8, 656, 10.1038/nrcardio.2011.120 Groenke, 2013, Complete atrial-specific knockout of sodium–calcium exchange eliminates sinoatrial node pacemaker activity, PLoS ONE, 8, e81633, 10.1371/journal.pone.0081633 Mesirca, 2015, Functional role of voltage gated Ca(2+) channels in heart automaticity, Front. Physiol., 6, 19, 10.3389/fphys.2015.00019 Baruscotti, 2011, Deep bradycardia and heart block caused by inducible cardiac-specific knockout of the pacemaker channel gene Hcn4, Proc. Natl. Acad. Sci. U.S.A., 108, 1705, 10.1073/pnas.1010122108 Lakatta, 2010, A coupled SYSTEM of intracellular Ca2+ clocks and surface membrane voltage clocks controls the timekeeping mechanism of the heart's pacemaker, Circ. Res., 106, 659, 10.1161/CIRCRESAHA.109.206078 Garcia-Frigola, 2003, Expression of the hyperpolarization-activated cyclic nucleotide-gated cation channel HCN4 during mouse heart development, Gene Expr. Patterns, 3, 777, 10.1016/S1567-133X(03)00125-X Milanesi, 2006, Familial sinus bradycardia associated with a mutation in the cardiac pacemaker channel, N. Engl. J. Med., 354, 151, 10.1056/NEJMoa052475 Verheijck, 2001, Electrophysiological features of the mouse sinoatrial node in relation to connexin distribution, Cardiovasc. Res., 52, 40, 10.1016/S0008-6363(01)00364-9 Morris, 2014, Fibrosis, electrics and genetics. Perspectives in sinoatrial node disease, Circ. J., 78, 1272, 10.1253/circj.CJ-14-0419 Bressan, 2013, Early mesodermal cues assign avian cardiac pacemaker fate potential in a tertiary heart field, Science, 340, 744, 10.1126/science.1232877 Mommersteeg, 2007, Molecular pathway for the localized formation of the sinoatrial node, Circ. Res., 100, 354, 10.1161/01.RES.0000258019.74591.b3 Viragh, 1980, The development of the conduction system in the mouse embryo heart, Dev. Biol., 80, 28, 10.1016/0012-1606(80)90496-0 Mommersteeg, 2010, The sinus venosus progenitors separate and diversify from the first and second heart fields early in development, Cardiovasc. Res., 87, 92, 10.1093/cvr/cvq033 Vedantham, 2015, RNA sequencing of mouse sinoatrial node reveals an upstream regulatory role for islet-1 in cardiac pacemaker cells, Circ. Res., 116, 797, 10.1161/CIRCRESAHA.116.305913 Wiese, 2009, Formation of the sinus node head and differentiation of sinus node myocardium are independently regulated by Tbx18 and Tbx3, Circ. Res., 104, 388, 10.1161/CIRCRESAHA.108.187062 Kapoor, 2011, Transcriptional suppression of connexin43 by TBX18 undermines cell-cell electrical coupling in postnatal cardiomyocytes, J. Biol. Chem., 286, 14073, 10.1074/jbc.M110.185298 Kapoor, 2013, Direct conversion of quiescent cardiomyocytes to pacemaker cells by expression of Tbx18, Nat. Biotechnol., 31, 54, 10.1038/nbt.2465 Hoogaars, 2007, Tbx3 controls the sinoatrial node gene program and imposes pacemaker function on the atria, Genes Dev., 21, 1098, 10.1101/gad.416007 Frank, 2012, Lethal arrhythmias in Tbx3-deficient mice reveal extreme dosage sensitivity of cardiac conduction system function and homeostasis, Proc. Natl. Acad. Sci. U.S.A., 109, E154, 10.1073/pnas.1115165109 Espinoza-Lewis, 2009, Shox2 is essential for the differentiation of cardiac pacemaker cells by repressing Nkx2-5, Dev. Biol., 327, 376, 10.1016/j.ydbio.2008.12.028 Blaschke, 2007, Targeted mutation reveals essential functions of the homeodomain transcription factor Shox2 in sinoatrial and pacemaking development, Circulation, 115, 1830, 10.1161/CIRCULATIONAHA.106.637819 Ye, 2015, A common Shox2-Nkx2-5 antagonistic mechanism primes the pacemaking cell fate in the pulmonary vein myocardium and sinoatrial node, Development, 142, 2521, 10.1242/dev.120220 Sun, 2015, The short stature homeobox 2 (Shox2)-bone morphogenetic protein (BMP) pathway regulates dorsal mesenchymal protrusion development and its temporary function as a pacemaker during cardiogenesis, J. Biol. Chem., 290, 2007, 10.1074/jbc.M114.619007 Cai, 2003, Isl1 identifies a cardiac progenitor population that proliferates prior to differentiation and contributes a majority of cells to the heart, Dev. Cell, 5, 877, 10.1016/S1534-5807(03)00363-0 Weinberger, 2012, Localization of Islet-1-positive cells in the healthy and infarcted adult murine heart, Circ. Res., 110, 1303, 10.1161/CIRCRESAHA.111.259630 Liang, 2015, Transcription factor ISL1 is essential for pacemaker development and function, J. Clin. Invest., 125, 3256, 10.1172/JCI68257 Satin, 2004, Mechanism of spontaneous excitability in human embryonic stem cell derived cardiomyocytes, J. Physiol., 559, 479, 10.1113/jphysiol.2004.068213 Kehat, 2004, Electromechanical integration of cardiomyocytes derived from human embryonic stem cells, Nat. Biotechnol., 22, 1282, 10.1038/nbt1014 Vedantham, 2013, Spatiotemporal regulation of an Hcn4 enhancer defines a role for Mef2c and HDACs in cardiac electrical patterning, Dev. Biol., 373, 149, 10.1016/j.ydbio.2012.10.017 Morikawa, 2010, Identification, isolation and characterization of HCN4-positive pacemaking cells derived from murine embryonic stem cells during cardiac differentiation, Pacing Clin. Electrophysiol., 33, 290, 10.1111/j.1540-8159.2009.02614.x Hashem, 2013, Genetic isolation of stem cell-derived pacemaker-nodal cardiac myocytes, Mol. Cell. Biochem., 383, 161, 10.1007/s11010-013-1764-x Hashem, 2013, Shox2 regulates the pacemaker gene program in embryoid bodies, Stem Cells Dev., 22, 2915, 10.1089/scd.2013.0123 Scavone, 2013, Embryonic stem cell-derived CD166+ precursors develop into fully functional sinoatrial-like cells, Circ. Res., 113, 389, 10.1161/CIRCRESAHA.113.301283 Ieda, 2010, Direct reprogramming of fibroblasts into functional cardiomyocytes by defined factors, Cell, 142, 375, 10.1016/j.cell.2010.07.002 Qian, 2012, In vivo reprogramming of murine cardiac fibroblasts into induced cardiomyocytes, Nature, 485, 593, 10.1038/nature11044 Song, 2012, Heart repair by reprogramming non-myocytes with cardiac transcription factors, Nature, 485, 599, 10.1038/nature11139 Bakker, 2012, T-box transcription factor TBX3 reprogrammes mature cardiac myocytes into pacemaker-like cells, Cardiovasc. Res., 94, 439, 10.1093/cvr/cvs120 Jung, 2014, Programming and isolation of highly pure physiologically and pharmacologically functional sinus-nodal bodies from pluripotent stem cells, Stem Cell Rep., 2, 592, 10.1016/j.stemcr.2014.03.006 Ionta, 2015, SHOX2 overexpression favors differentiation of embryonic stem cells into cardiac pacemaker cells, improving biological pacing ability, Stem Cell Rep., 4, 129, 10.1016/j.stemcr.2014.11.004 Hu, 2014, Biological pacemaker created by minimally invasive somatic reprogramming in pigs with complete heart block, Sci. Transl. Med., 6, 245ra94, 10.1126/scitranslmed.3008681 Laugwitz, 2005, Postnatal isl1+ cardioblasts enter fully differentiated cardiomyocyte lineages, Nature, 433, 647, 10.1038/nature03215 Moretti, 2006, Multipotent embryonic isl1+ progenitor cells lead to cardiac, smooth muscle, and endothelial cell diversification, Cell, 127, 1151, 10.1016/j.cell.2006.10.029 Dorn, 2015, Direct nkx2-5 transcriptional repression of isl1 controls cardiomyocyte subtype identity, Stem Cells, 33, 1113, 10.1002/stem.1923 Nam, 2014, Induction of diverse cardiac cell types by reprogramming fibroblasts with cardiac transcription factors, Development, 141, 4267, 10.1242/dev.114025 Takahashi, 2006, Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors, Cell, 126, 663, 10.1016/j.cell.2006.07.024 Takahashi, 2007, Induction of pluripotent stem cells from adult human fibroblasts by defined factors, Cell, 131, 861, 10.1016/j.cell.2007.11.019 Yasui, 2001, I(f) current and spontaneous activity in mouse embryonic ventricular myocytes, Circ. Res., 88, 536, 10.1161/01.RES.88.5.536 Udo, 2013, Long term quality-of-life in patients with bradycardia pacemaker implantation, Int. J. Cardiol., 168, 2159, 10.1016/j.ijcard.2013.01.253 Wilhelm, 2015, Complications and risk assessment of 25 years in pediatric pacing, Ann. Thorac. Surg., 100, 147, 10.1016/j.athoracsur.2014.12.098 Ye, 2015, A common Shox2-Nkx2-5 antagonistic mechanism primes the pacemaker cell fate in the pulmonary vein myocardium and sinoatrial node, Development, 142, 2521, 10.1242/dev.120220 Fu, 2013, Direct reprogramming of human fibroblasts toward a cardiomyocyte-like state, Stem Cell Rep., 1, 235, 10.1016/j.stemcr.2013.07.005 Rentschler, 2012, Myocardial Notch signaling reprograms cardiomyocytes to a conduction-like phenotype, Circulation, 126, 1058, 10.1161/CIRCULATIONAHA.112.103390 Tsai, 2015, Efficient generation of cardiac Purkinje cells from ESCs by activating cAMP signaling, Stem Cell Rep., 4, 1089, 10.1016/j.stemcr.2015.04.015 Maass, 2015, Isolation and characterization of embryonic stem cell-derived cardiac Purkinje cells, Stem Cells, 33, 1102, 10.1002/stem.1921 Hirata, 2006, ALCAM (CD166) is a surface marker for early murine cardiomyocytes, Cells Tissues Organs, 184, 172, 10.1159/000099624