TY - JOUR
T1 - Transcriptome profile of the sinoatrial ring reveals conserved and novel genetic programs of the zebrafish pacemaker
AU - Minhas, Rashid
AU - Loeffler-Wirth, Henry
AU - Siddiqui, Yusra H
AU - Obrębski, Tomasz
AU - Vashisht, Shikha
AU - Nahia, Karim Abu
AU - Paterek, Alexandra
AU - Brzozowska, Angelika
AU - Bugajski, Lukasz
AU - Piwocka, Katarzyna
AU - Korzh, Vladimir
AU - Binder, Hans
AU - Winata, Cecilia Lanny
N1 - Funding Information:
Research reported in this publication was supported by the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 665778, the fellowship registration number: 2015/19/P/NZ3/03613, supported by National Science Centre (NCN), Poland, for R.M.; the Opus Grant 2016/21/B/NZ3/00354 from the National Science Centre Poland for V.K.; the Opus Grant 2018/29/B/NZ2/01010 from the National Science Centre, Poland for S.V. Microscopy, sequencing data acquisition and functional analyses was supported by the following funder: The project no. POIR.04.04.00–00-1AF0/16–00/ is carried out within the First TEAM programme of the Foundation for Polish Science co-financed by the European Union under the European Regional Development Fund. The funding bodies played no role in the design of the study and collection, analysis, and interpretation of data and in writing the manuscript.
Publisher Copyright:
© 2021, The Author(s).
PY - 2021/10/2
Y1 - 2021/10/2
N2 - BACKGROUND: Sinoatrial Node (SAN) is part of the cardiac conduction system, which controls the rhythmic contraction of the vertebrate heart. The SAN consists of a specialized pacemaker cell population that has the potential to generate electrical impulses. Although the SAN pacemaker has been extensively studied in mammalian and teleost models, including the zebrafish, their molecular nature remains inadequately comprehended.RESULTS: To characterize the molecular profile of the zebrafish sinoatrial ring (SAR) and elucidate the mechanism of pacemaker function, we utilized the transgenic line sqet33mi59BEt to isolate cells of the SAR of developing zebrafish embryos and profiled their transcriptome. Our analyses identified novel candidate genes and well-known conserved signaling pathways involved in pacemaker development. We show that, compared to the rest of the heart, the zebrafish SAR overexpresses several mammalian SAN pacemaker signature genes, which include hcn4 as well as those encoding calcium- and potassium-gated channels. Moreover, genes encoding components of the BMP and Wnt signaling pathways, as well as members of the Tbx family, which have previously been implicated in pacemaker development, were also overexpressed in the SAR. Among SAR-overexpressed genes, 24 had human homologues implicated in 104 different ClinVar phenotype entries related to various forms of congenital heart diseases, which suggest the relevance of our transcriptomics resource to studying human heart conditions. Finally, functional analyses of three SAR-overexpressed genes, pard6a, prom2, and atp1a1a.2, uncovered their novel role in heart development and physiology.CONCLUSION: Our results established conserved aspects between zebrafish and mammalian pacemaker function and revealed novel factors implicated in maintaining cardiac rhythm. The transcriptome data generated in this study represents a unique and valuable resource for the study of pacemaker function and associated heart diseases.
AB - BACKGROUND: Sinoatrial Node (SAN) is part of the cardiac conduction system, which controls the rhythmic contraction of the vertebrate heart. The SAN consists of a specialized pacemaker cell population that has the potential to generate electrical impulses. Although the SAN pacemaker has been extensively studied in mammalian and teleost models, including the zebrafish, their molecular nature remains inadequately comprehended.RESULTS: To characterize the molecular profile of the zebrafish sinoatrial ring (SAR) and elucidate the mechanism of pacemaker function, we utilized the transgenic line sqet33mi59BEt to isolate cells of the SAR of developing zebrafish embryos and profiled their transcriptome. Our analyses identified novel candidate genes and well-known conserved signaling pathways involved in pacemaker development. We show that, compared to the rest of the heart, the zebrafish SAR overexpresses several mammalian SAN pacemaker signature genes, which include hcn4 as well as those encoding calcium- and potassium-gated channels. Moreover, genes encoding components of the BMP and Wnt signaling pathways, as well as members of the Tbx family, which have previously been implicated in pacemaker development, were also overexpressed in the SAR. Among SAR-overexpressed genes, 24 had human homologues implicated in 104 different ClinVar phenotype entries related to various forms of congenital heart diseases, which suggest the relevance of our transcriptomics resource to studying human heart conditions. Finally, functional analyses of three SAR-overexpressed genes, pard6a, prom2, and atp1a1a.2, uncovered their novel role in heart development and physiology.CONCLUSION: Our results established conserved aspects between zebrafish and mammalian pacemaker function and revealed novel factors implicated in maintaining cardiac rhythm. The transcriptome data generated in this study represents a unique and valuable resource for the study of pacemaker function and associated heart diseases.
KW - Animals
KW - Heart Rate
KW - Humans
KW - Pacemaker, Artificial
KW - Sinoatrial Node
KW - Transcriptome
KW - Zebrafish/genetics
KW - RNA-seq
UR - http://www.scopus.com/inward/record.url?scp=85116339330&partnerID=8YFLogxK
U2 - 10.1186/s12864-021-08016-z
DO - 10.1186/s12864-021-08016-z
M3 - Article
C2 - 34600492
SN - 1471-2164
VL - 22
SP - 715
JO - BMC GENOMICS
JF - BMC GENOMICS
IS - 1
M1 - 715
ER -
