title: Chamber Specific Gene Expression Landscape of the Zebrafish Heart.
abstract: The organization of structure and function of cardiac chambers in vertebrates is defined by chamber-specific distinct gene expression. This peculiarity and uniqueness of the genetic signatures demonstrates functional resolution attributed to the different chambers of the heart. Altered expression of the cardiac chamber genes can lead to individual chamber related dysfunctions and disease patho-physiologies. Information on transcriptional repertoire of cardiac compartments is important to understand the spectrum of chamber specific anomalies. We have carried out a genome wide transcriptome profiling study of the three cardiac chambers in the zebrafish heart using RNA sequencing. We have captured the gene expression patterns of 13,396 protein coding genes in the three cardiac chambers-atrium, ventricle and bulbus arteriosus. Of these, 7,260 known protein coding genes are highly expressed (≥10 FPKM) in the zebrafish heart. Thus, this study represents nearly an all-inclusive information on the zebrafish cardiac transcriptome. In this study, a total of 96 differentially expressed genes across the three cardiac chambers in zebrafish were identified. The atrium, ventricle and bulbus arteriosus displayed 20, 32 and 44 uniquely expressing genes respectively. We validated the expression of predicted chamber-restricted genes using independent semi-quantitative and qualitative experimental techniques. In addition, we identified 23 putative novel protein coding genes that are specifically restricted to the ventricle and not in the atrium or bulbus arteriosus. In our knowledge, these 23 novel genes have either not been investigated in detail or are sparsely studied. The transcriptome identified in this study includes 68 differentially expressing zebrafish cardiac chamber genes that have a human ortholog. We also carried out spatiotemporal gene expression profiling of the 96 differentially expressed genes throughout the three cardiac chambers in 11 developmental stages and 6 tissue types of zebrafish. We hypothesize that clustering the differentially expressed genes with both known and unknown functions will deliver detailed insights on fundamental gene networks that are important for the development and specification of the cardiac chambers. It is also postulated that this transcriptome atlas will help utilize zebrafish in a better way as a model for studying cardiac development and to explore functional role of gene networks in cardiac disease pathogenesis.
authors.affiliation: Genomics and Molecular Medicine, CSIR Institute of Genomics and Integrative Biology, Mathura Road, Delhi 110025, India.
authors.forename: Angom Ramcharan
authors.initials: AR
authors.lastname: Singh
authors.affiliation: GN Ramachandran Knowledge Center for Genome Informatics, CSIR Institute of Genomics and Integrative Biology, Mathura Road, Delhi 110025, India.|Academy of Scientific and Innovative Research, CSIR-IGIB South Campus, Mathura Road, Delhi 110025, India.
authors.forename: Ambily
authors.initials: A
authors.lastname: Sivadas
authors.affiliation: Genomics and Molecular Medicine, CSIR Institute of Genomics and Integrative Biology, Mathura Road, Delhi 110025, India.|Academy of Scientific and Innovative Research, CSIR-IGIB South Campus, Mathura Road, Delhi 110025, India.
authors.forename: Ankit
authors.initials: A
authors.lastname: Sabharwal
authors.affiliation: Genomics and Molecular Medicine, CSIR Institute of Genomics and Integrative Biology, Mathura Road, Delhi 110025, India.|Academy of Scientific and Innovative Research, CSIR-IGIB South Campus, Mathura Road, Delhi 110025, India.
authors.forename: Shamsudheen Karuthedath
authors.initials: SK
authors.lastname: Vellarikal
authors.affiliation: Genomics and Molecular Medicine, CSIR Institute of Genomics and Integrative Biology, Mathura Road, Delhi 110025, India.
authors.forename: Rijith
authors.initials: R
authors.lastname: Jayarajan
authors.affiliation: Genomics and Molecular Medicine, CSIR Institute of Genomics and Integrative Biology, Mathura Road, Delhi 110025, India.
authors.forename: Ankit
authors.initials: A
authors.lastname: Verma
authors.affiliation: Genomics and Molecular Medicine, CSIR Institute of Genomics and Integrative Biology, Mathura Road, Delhi 110025, India.|Academy of Scientific and Innovative Research, CSIR-IGIB South Campus, Mathura Road, Delhi 110025, India.
authors.forename: Shruti
authors.initials: S
authors.lastname: Kapoor
authors.affiliation: Genomics and Molecular Medicine, CSIR Institute of Genomics and Integrative Biology, Mathura Road, Delhi 110025, India.
authors.forename: Adita
authors.initials: A
authors.lastname: Joshi
authors.affiliation: GN Ramachandran Knowledge Center for Genome Informatics, CSIR Institute of Genomics and Integrative Biology, Mathura Road, Delhi 110025, India.|Academy of Scientific and Innovative Research, CSIR-IGIB South Campus, Mathura Road, Delhi 110025, India.
authors.forename: Vinod
authors.initials: V
authors.lastname: Scaria
authors.affiliation: Genomics and Molecular Medicine, CSIR Institute of Genomics and Integrative Biology, Mathura Road, Delhi 110025, India.|Academy of Scientific and Innovative Research, CSIR-IGIB South Campus, Mathura Road, Delhi 110025, India.
authors.forename: Sridhar
authors.initials: S
authors.lastname: Sivasubbu
mesh_terms: D000818:Animals; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D006325:Heart Atria / Q000254:growth & development / Q000378:metabolism*; D006352:Heart Ventricles / Q000254:growth & development / Q000378:metabolism*; D006801:Humans; D017403:In Situ Hybridization; D017423:Sequence Analysis, RNA; D059467:Transcriptome; D015027:Zebrafish / Q000235:genetics*; D029961:Zebrafish Proteins / Q000235:genetics*
chemical_list: D029961:Zebrafish Proteins
references.citation: PLoS One. 2013;8(2):e57800
references.pmid: 23460909
references.citation: Zebrafish. 2013 Mar;10(1):15-20
references.pmid: 23590399
references.citation: Development. 2013 Jul;140(13):2828-34
references.pmid: 23698349
references.citation: Nucleic Acids Res. 2013 Jul;41(Web Server issue):W77-83
references.pmid: 23703215
references.citation: PLoS One. 2013;8(10):e77492
references.pmid: 24147006
references.citation: PLoS One. 2013;8(10):e77938
references.pmid: 24205036
references.citation: Genet Mol Res. 2013;12(4):4687-97
references.pmid: 24222245
references.citation: PLoS One. 2013;8(12):e83616
references.pmid: 24391796
references.citation: BMC Cardiovasc Disord. 2014;14:10
references.pmid: 24461008
references.citation: Int Heart J. 2014;55(1):71-7
references.pmid: 24463922
references.citation: Circulation. 2014 Mar 4;129(9):1009-21
references.pmid: 24429688
references.citation: Gene. 2014 Jun 10;543(1):15-21
references.pmid: 24726549
references.citation: Mol Hum Reprod. 2014 Jul;20(7):690-700
references.pmid: 24674993
references.citation: Bioinformatics. 2014 Aug 1;30(15):2114-20
references.pmid: 24695404
references.citation: Genome Biol. 2013;14(4):R36
references.pmid: 23618408
references.citation: Cell Biochem Biophys. 2014 Sep;70(1):635-42
references.pmid: 24756729
references.citation: Nat Cell Biol. 2014 Sep;16(9):829-40
references.pmid: 25150979
references.citation: Curr Protoc Bioinformatics. 2014;47:11.12.1-34
references.pmid: 25199790
references.citation: BMC Genomics. 2014;15:852
references.pmid: 25280539
references.citation: J Biol Chem. 2014 Oct 24;289(43):29665-76
references.pmid: 25183011
references.citation: BMC Genomics. 2014;15:1127
references.pmid: 25516202
references.citation: Cell Physiol Biochem. 2015;35(2):467-76
references.pmid: 25613478
references.citation: Genomics. 2015 Feb;105(2):83-9
references.pmid: 25528681
references.citation: BMC Bioinformatics. 2015;16:74
references.pmid: 25887857
references.citation: Circ Cardiovasc Genet. 2015 Apr;8(2):261-9
references.pmid: 25583992
references.citation: Genesis. 2015 Aug;53(8):498-509
references.pmid: 26097180
references.citation: J Mol Cell Cardiol. 2010 Jan;48(1):161-71
references.pmid: 19747484
references.citation: Nat Genet. 2008 Dec;40(12):1413-5
references.pmid: 18978789
references.citation: Nat Rev Genet. 2009 Jan;10(1):57-63
references.pmid: 19015660
references.citation: Dev Dyn. 2009 Jun;238(6):1564-73
references.pmid: 19322764
references.citation: Hum Mutat. 2009 Sep;30(9):1267-77
references.pmid: 19562689
references.citation: N Engl J Med. 2010 Oct 28;363(18):1693-703
references.pmid: 20979469
references.citation: Nat Genet. 2011 Apr;43(4):316-20
references.pmid: 21378987
references.citation: Nature. 2011 May 19;473(7347):326-35
references.pmid: 21593865
references.citation: BMC Biol. 2011;9:34
references.pmid: 21627854
references.citation: Bioinformatics. 2011 Jul 1;27(13):i275-82
references.pmid: 21685081
references.citation: Cardiovasc Res. 2011 Jul 15;91(2):279-88
references.pmid: 21602174
references.citation: Nature. 2011 Oct 6;478(7367):57-63
references.pmid: 21937992
references.citation: PLoS Comput Biol. 2011 Oct;7(10):e1002195
references.pmid: 22039361
references.citation: Cell. 2011 Nov 11;147(4):789-802
references.pmid: 22056041
references.citation: Nucleic Acids Res. 2012 Jan;40(Database issue):D290-301
references.pmid: 22127870
references.citation: PLoS One. 2011;6(12):e28872
references.pmid: 22194935
references.citation: Cell. 2011 Dec 23;147(7):1537-50
references.pmid: 22196729
references.citation: Genome Res. 2012 Mar;22(3):577-91
references.pmid: 22110045
references.citation: Nat Methods. 2012 Apr;9(4):357-9
references.pmid: 22388286
references.citation: PLoS Genet. 2012;8(3):e1002584
references.pmid: 22479191
references.citation: Nucleic Acids Res. 2013 Jan;41(Database issue):D590-6
references.pmid: 23193283
references.citation: J Biol Chem. 2010 Apr 16;285(16):12344-54
references.pmid: 20139090
references.citation: Nat Biotechnol. 2010 May;28(5):511-5
references.pmid: 20436464
references.citation: BMC Bioinformatics. 2010;11:485
references.pmid: 20875133
references.citation: Dev Dyn. 2010 Nov;239(11):3115-23
references.pmid: 20925115
references.citation: Trends Genet. 2000 Jun;16(6):276-7
references.pmid: 10827456
references.citation: Hum Mol Genet. 2000 Aug 12;9(13):2051-8
references.pmid: 10942434
references.citation: N Engl J Med. 2000 Dec 7;343(23):1688-96
references.pmid: 11106718
references.citation: J Biol Chem. 2000 Dec 1;275(48):38073-80
references.pmid: 10970890
references.citation: Cell. 2001 Feb 23;104(4):557-67
references.pmid: 11239412
references.citation: Hum Mutat. 2001 Jun;17(6):524
references.pmid: 11385718
references.citation: Dev Biol. 2001 Nov 15;239(2):190-203
references.pmid: 11784028
references.citation: Circulation. 2002 Jan 29;105(4):446-51
references.pmid: 11815426
references.citation: Nucleic Acids Res. 2001 May 1;29(9):e45
references.pmid: 11328886
references.citation: Physiol Genomics. 2002 Dec 26;12(1):53-60
references.pmid: 12502795
references.citation: Circulation. 2003 Jan 28;107(3):469-76
references.pmid: 12551873
references.citation: Circulation. 2003 May 20;107(19):2467-74
references.pmid: 12742993
references.citation: Anat Rec A Discov Mol Cell Evol Biol. 2003 Jul;273(1):603-8
references.pmid: 12808645
references.citation: J Surg Res. 2003 May 1;111(1):152-7
references.pmid: 12842460
references.citation: Development. 2003 Dec;130(24):6121-9
references.pmid: 14573521
references.citation: Circ Res. 2003 Dec 12;93(12):1193-201
references.pmid: 14576202
references.citation: Fed Proc. 1986 Oct;45(11):2568-72
references.pmid: 3758376
references.citation: J Biol Chem. 1991 Sep 25;266(27):18058-65
references.pmid: 1917943
references.citation: N Engl J Med. 1995 Apr 20;332(16):1058-64
references.pmid: 7898523
references.citation: Genomics. 1996 Nov 1;37(3):281-8
references.pmid: 8938439
references.citation: Nature. 1998 Feb 12;391(6668):691-5
references.pmid: 9490411
references.citation: Annu Rev Physiol. 1998;60:287-308
references.pmid: 9558465
references.citation: Dev Biol. 2000 Jan 15;217(2):266-77
references.pmid: 10625552
references.citation: Cardiovasc Res. 1998 Apr;38(1):25-53
references.pmid: 9683906
references.citation: Science. 1999 Feb 19;283(5405):1161-4
references.pmid: 10024241
references.citation: Nat Genet. 1999 Mar;21(3):271-7
references.pmid: 10080178
references.citation: Methods Cell Biol. 2004;77:505-19
references.pmid: 15602929
references.citation: J Am Coll Cardiol. 2004 Dec 21;44(12):2315-25
references.pmid: 15607392
references.citation: Nucleic Acids Res. 2005 Jan 1;33(Database issue):D514-7
references.pmid: 15608251
references.citation: Nat Genet. 2005 Apr;37(4):423-8
references.pmid: 15735645
references.citation: Circulation. 2005 Jul 5;112(1):54-9
references.pmid: 15998695
references.citation: Circ Res. 2007 Mar 30;100(6):766-8
references.pmid: 17347475
references.citation: Biochim Biophys Acta. 2007 Jun;1773(6):804-13
references.pmid: 17459496
references.citation: Nucleic Acids Res. 2007 Jul;35(Web Server issue):W345-9
references.pmid: 17631615
references.citation: Nat Protoc. 2008;3(1):59-69
references.pmid: 18193022
references.citation: J Biol Chem. 2008 Apr 25;283(17):11850-9
references.pmid: 18310078
references.citation: Nat Methods. 2008 Jul;5(7):585-7
references.pmid: 18587314
references.citation: Clin Cancer Res. 2008 Jul 1;14(13):4275-83
references.pmid: 18594010
references.citation: Science. 2008 Aug 15;321(5891):956-60
references.pmid: 18599741
references.citation: Bioinformatics. 2013 Jan 1;29(1):15-21
references.pmid: 23104886