TY - JOUR
T1 - Spatially resolved RNA-sequencing of the embryonic heart identifies a role for Wnt/β-catenin signaling in autonomic control of heart rate
AU - Burkhard, Silja Barbara
AU - Bakkers, Jeroen
N1 - Funding Information:
We thank Utrecht Sequencing Facility for providing the sequencing service and data. Utrecht Sequencing Facility is subsidized by the University Medical Center Utrecht, Hubrecht Institute and Utrecht University. We thank Fabian Kruse for bioinformatics support, Laurence Garric for discussions during the project, Federico Tessadori for help with the BAC transgenesis, Kelly Smith for help with the tg(7xTCF-nlsmCherry) analysis, the Hubrecht Imaging Facility for microscopy support and Life Science Editors for editing support. We acknowledge support from the Netherlands Cardiovascular Research Initiative, Dutch Heart Foundation grant CVON2014-18 CONCOR-GENES, CVON Predict, ZonMW grant 40-00812-98-12086, and the ERA-NET Cofund action N° 643578 under the European Union’s Horizon 2020 research and innovation programme and national funding organisations Canadian Institutes for Health Research (CIHR), the Netherlands Organization for Health Research and Development (ZonMw), Belgium (Flanders) Research Foundation Flanders (FWO), and French National Research Agency (ANR). Nederlandse Organisatie voor Wetenschappelijk Onderzoek 022.001.003 Silja Barbara Burkhard CVON - Netherlands Heart Foundation CVON-CONCORgenes Jeroen Bakkers ZonMw 91212086 Jeroen Bakkers ZonMw 9003037607 Jeroen Bakkers.
Funding Information:
We thank Utrecht Sequencing Facility for providing the sequencing service and data. Utrecht Sequencing Facility is subsidized by the University Medical Center Utrecht, Hubrecht Institute and Utrecht University. We thank Fabian Kruse for bioinformatics support, Laurence Garric for discussions during the project, Federico Tessadori for help with the BAC transgenesis, Kelly Smith for help with the tg(7xTCF-nlsmCherry) analysis, the Hubrecht Imaging Facility for microscopy support and Life Science Editors for editing support. We acknowledge support from the Netherlands Cardiovascular Research Initiative, Dutch Heart Foundation grant CVON2014-18 CONCOR-GENES, CVON Predict, ZonMWgrant40-00812-98-12086,andtheERA-NETCofundactionN˚ 643578 under the European Union’s Horizon 2020 research and innovation programme and national funding organisations Canadian Institutes for Health Research (CIHR), the Netherlands Organization for Health Research and Development (ZonMw), Belgium (Flanders) Research Foundation Flanders (FWO), and French National Research Agency (ANR) .
Publisher Copyright:
© Burkhard and Bakkers.
PY - 2018/2/5
Y1 - 2018/2/5
N2 - Development of specialized cells and structures in the heart is regulated by spatially - restricted molecular pathways. Disruptions in these pathways can cause severe congenital cardiac malformations or functional defects. To better understand these pathways and how they regulate cardiac development we used tomo-seq, combining high-throughput RNA-sequencing with tissue- sectioning, to establish a genome-wide expression dataset with high spatial resolution for the developing zebrafish heart. Analysis of the dataset revealed over 1100 genes differentially expressed in sub-compartments. Pacemaker cells in the sinoatrial region induce heart contractions, but little is known about the mechanisms underlying their development. Using our transcriptome map, we identified spatially restricted Wnt/b-catenin signaling activity in pacemaker cells, which was controlled by Islet-1 activity. Moreover, Wnt/b-catenin signaling controls heart rate by regulating pacemaker cellular response to parasympathetic stimuli. Thus, this high-resolution transcriptome map incorporating all cell types in the embryonic heart can expose spatially restricted molecular pathways critical for specific cardiac functions.
AB - Development of specialized cells and structures in the heart is regulated by spatially - restricted molecular pathways. Disruptions in these pathways can cause severe congenital cardiac malformations or functional defects. To better understand these pathways and how they regulate cardiac development we used tomo-seq, combining high-throughput RNA-sequencing with tissue- sectioning, to establish a genome-wide expression dataset with high spatial resolution for the developing zebrafish heart. Analysis of the dataset revealed over 1100 genes differentially expressed in sub-compartments. Pacemaker cells in the sinoatrial region induce heart contractions, but little is known about the mechanisms underlying their development. Using our transcriptome map, we identified spatially restricted Wnt/b-catenin signaling activity in pacemaker cells, which was controlled by Islet-1 activity. Moreover, Wnt/b-catenin signaling controls heart rate by regulating pacemaker cellular response to parasympathetic stimuli. Thus, this high-resolution transcriptome map incorporating all cell types in the embryonic heart can expose spatially restricted molecular pathways critical for specific cardiac functions.
UR - https://www.scopus.com/pages/publications/85043522142
U2 - 10.7554/eLife.31515
DO - 10.7554/eLife.31515
M3 - Article
AN - SCOPUS:85043522142
SN - 2050-084X
VL - 7
JO - eLife
JF - eLife
M1 - e31515
ER -