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| Status |
Public on May 04, 2019 |
| Title |
Quantitative proteomic and single-nucleus transcriptomics map of the sinus node elucidates the foundation of cardiac pacemaking |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
The sinus node is a collection of highly specialised cells constituting the heart’s pacemaker. It is keenly debated whether the so-called membrane or alternatively Ca2+ clocks provide the molecular substrate of pacemaking. By high-resolution mass spectrometry, we quantified >7,000 proteins from sinus node and neighbouring atrial muscle. The abundances of 575 proteins differed between the two tissues, including particular differences in metabolic profiles and extracellular matrix composition. Most notably, the data reveal significant differences between the tissues in the ion channels responsible for the membrane clock, but not in Ca2+ clock proteins, suggesting that the membrane clock underpins pacemaking. By performing single-nucleus RNA sequencing of sinus node biopsies, we attributed protein abundances to specific cell types. Consistent with these results, incorporation of the ion channel expression differences into a biophysically-detailed atrial action potential model resulted in pacemaking and a sinus node-like action potential. Combining our quantitative proteomics data with computational modeling, we estimate ion channel copy numbers for sinus node myocytes. Our findings provide detailed insights into the unique molecular make-up of the pacemaker of the heart.
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| Overall design |
Single-nucleus transcriptomics using the 10X Genomics Chromium system.
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| Contributor(s) |
Schrölkamp M, Egerod KL, Thompson JJ, Pers TH, Lundby A |
| Citation(s) |
31253831 |
| Submission date |
May 03, 2019 |
| Last update date |
Jul 09, 2019 |
| Contact name |
Tune Hannes Pers |
| E-mail(s) |
tune.pers@sund.ku.dk
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| Organization name |
University of Copenhagen
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| Department |
Novo Nordisk Foundation Center for Basic Metabolic Research
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| Lab |
Tune Pers
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| Street address |
Blegdamsvej 3B
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| City |
Copenhagen |
| ZIP/Postal code |
2200 |
| Country |
Denmark |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (2) |
| GSM3748100 |
Single-nucleus from the sinus nodes of 8 mice (pooled) [H4_S1] |
| GSM3748101 |
Single-nucleus from the sinus nodes of 8 mice (pooled) [H5_S2] |
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| Relations |
| BioProject |
PRJNA541019 |
| SRA |
SRP194998 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE130710_metadata.csv.gz |
189.2 Kb |
(ftp)(http) |
CSV |
| GSE130710_normdata.csv.gz |
130.4 Mb |
(ftp)(http) |
CSV |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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