Transcription factor ISL1 is essential for pacemaker development and function

Journal of Clinical Investigation

Volumn 125, Issue 8, 2015, Pages 3256-3268

  Liang, Xingqun ^a   Zhang, Qingquan ^a   Cattaneo, Paola ^b   Zhuang, Shaowei ^a   Gong, Xiaohui ^a   Spann, Nathanael J ^b   Jiang, Cizhong ^c   Cao, Xinkai ^c   Zhao, Xiaodong ^d   Zhang, Xiaoli ^d   Bu, Lei ^b   Wang, Gang ^b   Chen, H S Vincent ^b   Zhuang, Tao ^a   Yan, Jie ^a   Geng, Peng ^a   Luo, Lina ^a   Banerjee, Indroneal ^b   Chen, Yihan ^a   Glass, Christopher K ^b,e   Zambon, Alexander C ^f   Chen, Ju ^b   Sun, Yunfu ^a   Evans, Sylvia M ^b   more..

^a TONGJI UNIVERSITY SCHOOL OF MEDICINE   (China)

^b UNIVERSITY OF CALIFORNIA   (United States)

^c TONGJI UNIVERSITY   (China)

^d SHANGHAI JIAO TONG UNIVERSITY   (China)

^e UNIVERSITY OF CALIFORNIA SAN DIEGO   (United States)

^f KECK GRADUATE INSTITUTE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BONE MORPHOGENETIC PROTEIN 4; CALCIUM CHANNEL L TYPE; GENOMIC DNA; HCN4 PROTEIN; HISTONE DEACETYLASE 7; ION CHANNEL; K RAS PROTEIN; MYC PROTEIN; PANTOTHENATE KINASE 2; POTASSIUM CHANNEL; PROTEIN; TRANSCRIPTION FACTOR; TRANSCRIPTION FACTOR ISL1; TRANSCRIPTION FACTOR TBX3; TROPONIN T; UNCLASSIFIED DRUG; ANK2 PROTEIN, MOUSE; ANKYRIN; CHROMATIN; INSULIN GENE ENHANCER BINDING PROTEIN ISL-1; LIM HOMEODOMAIN PROTEIN; PROTEIN BINDING; T BOX TRANSCRIPTION FACTOR; TBX3 PROTEIN, MOUSE;

ANIMAL CELL; ARTICLE; ATRIOVENTRICULAR CONDUCTION; CELL ADHESION; CELL FUNCTION; CELL MATURATION; CELL PROLIFERATION; CELL SURVIVAL; CHROMATIN; CHROMATIN IMMUNOPRECIPITATION; CONFORMATION; CONTROLLED STUDY; DNA BASE COMPOSITION; DNA BINDING MOTIF; EMBRYO; ENHANCER REGION; EXTRACELLULAR MATRIX; GENE DELETION; GENE EXPRESSION; HEART FUNCTION; HEART MUSCLE; HEART MUSCLE CELL; HEART MUSCLE CONDUCTION SYSTEM; HEART RATE VARIABILITY; HEART RHYTHM; NONHUMAN; PHENOTYPE; PRIORITY JOURNAL; PROMOTER REGION; RNA SEQUENCE; SICK SINUS SYNDROME; SINUS NODE; TRANSCRIPTION INITIATION SITE; UPREGULATION; VEIN VALVE; ANIMAL; CYTOLOGY; EMBRYOLOGY; GENE EXPRESSION REGULATION; GENETICS; HEART CONTRACTION; METABOLISM; MOUSE; PATHOLOGY; PHYSIOLOGY; TRANSGENIC MOUSE;

ANIMALS; ANKYRINS; CELL PROLIFERATION; CELL SURVIVAL; CHROMATIN; GENE DELETION; GENE EXPRESSION REGULATION, DEVELOPMENTAL; LIM-HOMEODOMAIN PROTEINS; MICE; MICE, TRANSGENIC; MYOCARDIAL CONTRACTION; PROTEIN BINDING; SICK SINUS SYNDROME; SINOATRIAL NODE; T-BOX DOMAIN PROTEINS; TRANSCRIPTION FACTORS;

EID: 84939225736     PISSN: 00219738     EISSN: 15588238     Source Type: Journal    
DOI: 10.1172/JCI68257     Document Type: Article

References (88)

1. Chugh SS, et al. Epidemiology of sudden cardiac death: clinical and research implications. Prog Cardiovasc Dis. 2008;51(3):213-228.
2. Lamas GA, et al. Ventricular pacing or dualchamber pacing for sinus-node dysfunction. N Engl J Med. 2002;346(24):1854-1862.
3. Dobrzynski H, Boyett MR, Anderson RH. New insights into pacemaker activity: promoting understanding of sick sinus syndrome. Circulation. 2007;115(14):1921-1932.
4. Gepstein L. Stem cells as biological heart pacemakers. Expert Opin Biol Ther. 2005;5(12):1531-1537.
5. 2+ clocks and surface membrane voltage clocks controls the timekeeping mechanism of the heart's pacemaker. Circ Res. 2010;106(4):659-673.
6. Mangoni ME, Nargeot J. Genesis and regulation of the heart automaticity. Physiol Rev. 2008;88(3):919-982.
7. 2+ cycling and surface membrane ion channel activation entrains normal automaticity in cells of the heart's pacemaker. Ann N Y Acad Sci. 2006;1080:178-206.
8. 2+ clock and membrane ion channel clock underlie robust initiation and regulation of cardiac pacemaker function. Cardiovasc Res. 2008;77(2):274-284.
9. Garcia-Frigola C, Shi Y, Evans SM. Expression of the hyperpolarization-activated cyclic nucleotide-gated cation channel HCN4 during mouse heart development. Gene Expr Patterns. 2003;3(6):777-783.
10. Ludwig A, Zong X, Jeglitsch M, Hofmann F, Biel M. A family of hyperpolarization-activated mammalian cation channels. Nature. 1998;393(6685):587-591.
11. Stieber J, et al. The hyperpolarization-activated channel HCN4 is required for the generation of pacemaker action potentials in the embryonic heart. Proc Natl Acad Sci U S A. 2003;100(25):15235-15240.
12. Laish-Farkash A, et al. A novel mutation in the HCN4 gene causes symptomatic sinus bradycardia in moroccan jews. J Cardiovasc Electrophysiol. 2010;21(12):1365-1372.
13. Ueda K, et al. Role of HCN4 channel in preventing ventricular arrhythmia. J Hum Genet. 2009;54(2):115-121.
14. Nof E, et al. Point mutation in the HCN4 cardiac ion channel pore affecting synthesis, trafficking, and functional expression is associated with familial asymptomatic sinus bradycardia. Circulation. 2007;116(5):463-470.
15. Milanesi R, Baruscotti M, Gnecchi-Ruscone T, DiFrancesco D. Familial sinus bradycardia associated with a mutation in the cardiac pacemaker channel. N Engl J Med. 2006;354(2):151-157.
16. Ueda K, et al. Functional characterization of a trafficking-defective HCN4 mutation, D553N, associated with cardiac arrhythmia. J Biol Chem. 2004;279(26):27194-27198.
17. Schulze-Bahr E, et al. Pacemaker channel dysfunction in a patient with sinus node disease. J Clin Invest. 2003;111(10):1537-1545.
18. Schweizer PA, et al. cAMP sensitivity of HCN pacemaker channels determines basal heart rate but is not critical for autonomic rate control. Circ Arrhythm Electrophysiol. 2010;3(5):542-552.
19. Herrmann S, Stieber J, Stockl G, Hofmann F, Ludwig A. HCN4 provides a 'depolarization reserve' and is not required for heart rate acceleration in mice. EMBO J. 2007;26(21):4423-4432.
20. 2+oscillations, a potential pacemaking mechanism in early embryonic heart cells. J Gen Physiol. 2007;130(2):133-144.
21. Yang HT, et al. The ryanodine receptor modulates the spontaneous beating rate of cardiomyocytes during development. Proc Natl Acad Sc U S A. 2002;99(14):9225-9230.
22. Koushik SV, et al. Targeted inactivation of the sodium-calcium exchanger (Ncx1) results in the lack of a heartbeat and abnormal myofibrillar organization. FASEB J. 2001;15(7):1209-1211.
23. Mangoni ME, Couette B, Marger L, Bourinet E, Striessnig J, Nargeot J. Voltage-dependent calcium channels and cardiac pacemaker activity: from ionic currents to genes. Prog Biophys Mol Biol. 2006;90(1-3):38-63.
24. Takeshima H, Komazaki S, Hirose K, Nishi M, Noda T, Iino M. Embryonic lethality and abnormal cardiac myocytes in mice lacking ryanodine receptor type 2. EMBO J. 1998;17(12):3309-3316.
25. Narayanan N, Xu A. Phosphorylation and regulation of the Ca(2+)-pumping ATPase in cardiac sarcoplasmic reticulum by calcium/calmodulin-dependent protein kinase. Basic Res Cardiol. 1997;92(suppl 1):25-35.
26. Meyer M, Dillmann WH. Sarcoplasmic reticulum Ca(2+)-ATPase overexpression by adenovirus mediated gene transfer and in transgenic mice. Cardiovasc Res. 1998;37(2):360-366.
27. Periasamy M, et al. Impaired cardiac performance in heterozygous mice with a null mutation in the sarco(endo)plasmic reticulum Ca2+-AT- Pase isoform 2 (SERCA2) gene. J Biol Chem. 1999;274(4):2556-2562.
28. Ver Heyen M, et al. Replacement of the muscle-specific sarcoplasmic reticulum Ca(2+)-AT- Pase isoform SERCA2a by the nonmuscle SERCA2b homologue causes mild concentric hypertrophy and impairs contraction-relaxation of the heart. Circ Res. 2001;89(9):838-846.
29. Hirota A, Fujii S, Kamino K. Optical monitoring of spontaneous electrical activity of 8-somite embryonic chick heart. Jpn J Physiol. 1979;29(5):635-639.
30. Kamino K, Hirota A, Fujii S. Localization of pacemaking activity in early embryonic heart monitored using voltage-sensitive dye. Nature. 1981;290(5807):595-597.
31. Van Mierop LH. Location of pacemaker in chick embryo heart at the time of initiation of heartbeat. Am J Physiol. 1967;212(2):407-415.
32. Viragh S, Challice CE. The development of the conduction system in the mouse embryo heart. Dev Biol. 1980;80(1):28-45.
33. Christoffels VM, et al. Formation of the venous pole of the heart from an Nkx2-5-negative precursor population requires Tbx18. Circ Res. 2006;98(12):1555-1563.
34. Wiese C, et al. Formation of the sinus node head and differentiation of sinus node myocardium are independently regulated by Tbx18 and Tbx3. Circ Res. 2009;104(3):388-397.
35. Kapoor N, Liang W, Marban E, Cho HC. Direct conversion of quiescent cardiomyocytes to pacemaker cells by expression of Tbx18. Nat Biotechnol. 2013;31(1):54-62.
36. Hoogaars WM, et al. Tbx3 controls the sinoatrial node gene program and imposes pacemaker function on the atria. Genes Dev. 2007;21(9):1098-1112.
37. Patel R, Kos L. Endothelin-1 and Neuregulin-1 convert embryonic cardiomyocytes into cells of the conduction system in the mouse. Dev Dyn. 2005;233(1):20-28.
38. Gourdie RG, Wei Y, Kim D, Klatt SC, Mikawa T. Endothelin-induced conversion of embryonic heart muscle cells into impulse-conducting Purkinje fibers. Proc Natl Acad Sci U S A. 1998;95(12):6815-6818.
39. Hyer J, et al. Induction of Purkinje fiber differentiation by coronary arterialization. Proc Natl Acad Sci U S A. 1999;96(23):13214-13218.
40. Rentschler S, et al. Neuregulin-1 promotes formation of the murine cardiac conduction system. Proc Natl Acad Sci U S A. 2002;99(16):10464-10469.
41. Milan DJ, Giokas AC, Serluca FC, Peterson RT, MacRae CA. Notch1b and neuregulin are required for specification of central cardiac conduction tissue. Development. 2006;133(6):1125-1132.
42. Rentschler S, et al. Notch signaling regulates murine atrioventricular conduction and the formation of accessory pathways. J Clin Invest. 2011;121(2):525-533.
43. Mommersteeg MT, et al. Molecular pathway for the localized formation of the sinoatrial node. Circ Res. 2007;100(3):354-362.
44. Christoffels VM, Smits GJ, Kispert A, Moorman AF. Development of the pacemaker tissues of the heart. Circ Res. 2010;106(2):240-254.
45. Hoogaars WM, et al. The transcriptional repressor Tbx3 delineates the developing central conduction system of the heart. Cardiovasc Res. 2004;62(3):489-499.
46. Frank DU, et al. Lethal arrhythmias in Tbx- 3-deficient mice reveal extreme dosage sensitivity of cardiac conduction system function and homeostasis. Proc Natl Acad Sci U S A. 2012;109(3):E154-E163.
47. Bakker ML, et al. T-box transcription factor TBX3 reprogrammes mature cardiac myocytes into pacemaker-like cells. Cardiovasc Res. 2012;94(3):439-449.
48. Hu YF, Dawkins JF, Cho HC, Marban E, Cingolani E. Biological pacemaker created by minimally invasive somatic reprogramming in pigs with complete heart block. Sci Transl Med. 2014;6(245):245ra94.
49. Blaschke RJ, et al. Targeted mutation reveals essential functions of the homeodomain transcription factor Shox2 in sinoatrial and pacemaking development. Circulation. 2007;115(14):1830-1838.
50. Espinoza-Lewis RA, et al. Shox2 is essential for the differentiation of cardiac pacemaker cells by repressing Nkx2-5. Dev Biol. 2009;327(2):376-385.
51. Liu H, et al. Functional redundancy between human SHOX and mouse Shox2 genes in the regulation of sinoatrial node formation and pacemaking function. J Biol Chem. 2011;286(19):17029-17038.
52. Cai CL, et al. Isl1 identifies a cardiac progenitor population that proliferates prior to differentiation and contributes a majority of cells to the heart. Dev Cell. 2003;5(6):877-889.
53. Moretti A, et al. Multipotent embryonic isl1+ progenitor cells lead to cardiac, smooth muscle, and endothelial cell diversification. Cell. 2006;127(6):1151-1165.
54. Sun Y, et al. Islet 1 is expressed in distinct cardiovascular lineages, including pacemaker and coronary vascular cells. Dev Biol. 2007;304(1):286-296.
55. Sizarov A, Devalla HD, Anderson RH, Passier R, Christoffels VM, Moorman AF. Molecular analysis of patterning of conduction tissues in the developing human heart. Circ Arrhythm Electrophysiol. 2011;4(4):532-542.
56. Mommersteeg MT, et al. The sinus venosus progenitors separate and diversify from the first and second heart fields early in development. Cardiovasc Res. 2010;87(1):92-101.
57. de Pater E, et al. Distinct phases of cardiomyocyte differentiation regulate growth of the zebrafish heart. Development. 2009;136(10):1633-1641.
58. Tessadori F, et al. Identification and functional characterization of cardiac pacemaker cells in zebrafish. PLoS One. 2012;7(10):e47644.
59. Hoffmann S, et al. Islet1 is a direct transcriptional target of the homeodomain transcription factor Shox2 and rescues the Shox2-mediated bradycardia. Basic Res Cardiol. 2013;108(2):339.
60. Vedantham V, Galang G, Evangelista M, Deo RC, Srivastava D. RNA sequencing of mouse sinoatrial node reveals an upstream regulatory role for islet-1 in cardiac pacemaker cells. Circ Res. 2015;116(5):797-803.
61. Liang X, et al. HCN4 dynamically marks the first heart field and conduction system precursors. Circ Res. 2013;113(4):399-407.
62. Spater D, et al. A HCN4+ cardiomyogenic progenitor derived from the first heart field and human pluripotent stem cells. Nat Cell Biol. 2013;15(9):1098-1106.
63. Liang X, et al. Isl1 is required for multiple aspects of motor neuron development. Mol Cell Neurosci. 2011;47(3):215-222.
64. Song MR, Sun Y, Bryson A, Gill GN, Evans SM, Pfaff SL. Islet-to-LMO stoichiometries control the function of transcription complexes that specify motor neuron and V2a interneuron identity. Development. 2009;136(17):2923-2932.
65. Jiao K, et al. An essential role of Bmp4 in the atrioventricular septation of the mouse heart. Genes Dev. 2003;17(19):2362-2367.
66. Hoesl E, et al. Tamoxifen-inducible gene deletion in the cardiac conduction system. J Mol Cell Cardiol. 2008;45(1):62-69.
67. Heinz S, et al. Effect of natural genetic variation on enhancer selection and function. Nature. 2013;503(7477):487-492.
68. Gosselin D, et al. Environment drives selection and function of enhancers controlling tissue-specific macrophage identities. Cell. 2014;159(6):1327-1340.
69. Le Scouarnec S, et al. Dysfunction in ankyrin-B-dependent ion channel and transporter targeting causes human sinus node disease. Proc Natl Acad Sci U S A. 2008;105(40):15617-15622.
70. Takeshita K, et al. Sinoatrial node dysfunction and early unexpected death of mice with a defect of klotho gene expression. Circulation. 2004;109(14):1776-1782.
71. van Weerd JH, et al. A large permissive regulatory domain exclusively controls Tbx3 expression in the cardiac conduction system. Circ Res. 2014;115(4):432-441.
72. Jin F, et al. A high-resolution map of the three-dimensional chromatin interactome in human cells. Nature. 2013;503(7475):290-294.
73. den Hoed M, et al. Identification of heart rate-associated loci and their effects on cardiac conduction and rhythm disorders. Nat Genet. 2013;45(6):621-631.
74. Bamshad M, et al. Mutations in human TBX3 alter limb, apocrine and genital development in ulnar-mammary syndrome. Nat Genet. 1997;16(3):311-315.
75. Zaki MS, et al. New recessive syndrome of micro-cephaly, cerebellar hypoplasia, and congenital heart conduction defect. Am J Med Genet Part A. 2011;155A(12):3035-3041.
76. Dackor RT, Fritz-Six K, Dunworth WP, Gibbons CL, Smithies O, Caron KM. Hydrops fetalis, cardiovascular defects, and embryonic lethality in mice lacking the calcitonin receptor-like receptor gene. Mol Cell Biol. 2006;26(7):2511-2518.
77. Yang XJ, Zhou YF, Li HX, Han LH, Jiang WP. Mesenchymal stem cells as a gene delivery system to create biological pacemaker cells in vitro. J Int Med Res. 2008;36(5):1049-1055.
78. Dorn T, et al. Direct nkx2-5 transcriptional repression of isl1 controls cardiomyocyte subtype identity. Stem Cells. 2015;33(4):1113-1129.
79. Sun Y, Dykes IM, Liang X, Eng SR, Evans SM, Turner EE. A central role for Islet1 in sensory neuron development linking sensory and spinal gene regulatory programs. Nat Neurosci. 2008;11(11):1283-1293.
80. Liang X, et al. PINCH1 plays an essential role in early murine embryonic development but is dispensable in ventricular cardiomyocytes. Mol Cell Biol. 2005;25(8):3056-3062.
81. Liang X, et al. Pinch1 is required for normal development of cranial and cardiac neural crest-derived structures. Circ Res. 2007;100(4):527-535.
82. Guo G, et al. Whole-genome and whole-exome sequencing of bladder cancer identifies frequent alterations in genes involved in sister chromatid cohesion and segregation. Nat Genet. 2013;45(12):1459-1463.
83. Kim D, Pertea G, Trapnell C, Pimentel H, Kelley R, Salzberg SL. TopHat2: accurate alignment of transcriptomes in the presence of insertions, deletions and gene fusions. Genome Biol. 2013;14(4):R36.
84. Langmead B, Salzberg SL. Fast gapped-read alignment with Bowtie 2. Nat Methods. 2012;9(4):357-359.
85. Salomonis N, et al. Alternative splicing regulates mouse embryonic stem cell pluripotency and differentiation. Proc Natl Acad Sci U S A. 2010;107(23):10514-10519.
86. Zambon AC, et al. GO-Elite: a flexible solution for pathway and ontology over-representation. Bioinformatics. 2012;28(16):2209-2210.
87. Li P, et al. NCoR repression of LXRs restricts macrophage biosynthesis of insulin-sensitizing omega 3 fatty acids. Cell. 2013;155(1):200-214.
88. Heinz S, et al. Simple combinations of lineage-determining transcription factors prime cis-regulatory elements required for macrophage and B cell identities. Mol Cell. 2010;38(4):576-589.