Quantitative proteomics and single-nucleus transcriptomics of the sinus node elucidates the foundation of cardiac pacemakingCitation formats

  • External authors:
  • Nora Linscheid
  • Pi Camilla Poulsen
  • Shanzhuo Zhang
  • Maren Schrölkamp
  • Kristoffer Lihme Egerod
  • Jonatan James Thompson
  • Henggui Zhang
  • Tune H. Pers
  • Jesper Velgaard Olsen
  • Alicia Lundby

Standard

Quantitative proteomics and single-nucleus transcriptomics of the sinus node elucidates the foundation of cardiac pacemaking. / Linscheid, Nora; Logantha, Sunil Jit R. J.; Poulsen, Pi Camilla; Zhang, Shanzhuo; Schrölkamp, Maren; Egerod, Kristoffer Lihme; Thompson, Jonatan James; Kitmitto, Ashraf; Galli, Gina; Humphries, Martin J.; Zhang, Henggui; Pers, Tune H.; Olsen, Jesper Velgaard; Boyett, Mark; Lundby, Alicia.

In: Nature Communications, Vol. 10, No. 1, 2019.

Research output: Contribution to journalArticle

Harvard

Linscheid, N, Logantha, SJRJ, Poulsen, PC, Zhang, S, Schrölkamp, M, Egerod, KL, Thompson, JJ, Kitmitto, A, Galli, G, Humphries, MJ, Zhang, H, Pers, TH, Olsen, JV, Boyett, M & Lundby, A 2019, 'Quantitative proteomics and single-nucleus transcriptomics of the sinus node elucidates the foundation of cardiac pacemaking', Nature Communications, vol. 10, no. 1. https://doi.org/10.1038/s41467-019-10709-9

APA

Linscheid, N., Logantha, S. J. R. J., Poulsen, P. C., Zhang, S., Schrölkamp, M., Egerod, K. L., ... Lundby, A. (2019). Quantitative proteomics and single-nucleus transcriptomics of the sinus node elucidates the foundation of cardiac pacemaking. Nature Communications, 10(1). https://doi.org/10.1038/s41467-019-10709-9

Vancouver

Author

Linscheid, Nora ; Logantha, Sunil Jit R. J. ; Poulsen, Pi Camilla ; Zhang, Shanzhuo ; Schrölkamp, Maren ; Egerod, Kristoffer Lihme ; Thompson, Jonatan James ; Kitmitto, Ashraf ; Galli, Gina ; Humphries, Martin J. ; Zhang, Henggui ; Pers, Tune H. ; Olsen, Jesper Velgaard ; Boyett, Mark ; Lundby, Alicia. / Quantitative proteomics and single-nucleus transcriptomics of the sinus node elucidates the foundation of cardiac pacemaking. In: Nature Communications. 2019 ; Vol. 10, No. 1.

Bibtex

@article{c04688051e28421c91fa4d486db37703,
title = "Quantitative proteomics and single-nucleus transcriptomics of the sinus node elucidates the foundation of cardiac pacemaking",
abstract = "The sinus node is a collection of highly specialised cells constituting the heart’s pacemaker. The molecular underpinnings of its pacemaking abilities are debated. By high-resolution mass spectrometry, we quantify >7,000 proteins from sinus node and neighbouring atrial muscle. Abundances of 575 proteins differ between the two tissues. By performing single-nucleus RNA sequencing of sinus node biopsies, we attribute measured protein abundances to specific cell types. The data reveals significant differences in ion channels responsible for the membrane clock, but not in Ca2+ clock proteins, suggesting that the membrane clock underpins pacemaking. Consistently, incorporation of ion channel expression differences into a biophysically-detailed atrial action potential model result 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 cardiac pacemaker.",
author = "Nora Linscheid and Logantha, {Sunil Jit R. J.} and Poulsen, {Pi Camilla} and Shanzhuo Zhang and Maren Schr{\"o}lkamp and Egerod, {Kristoffer Lihme} and Thompson, {Jonatan James} and Ashraf Kitmitto and Gina Galli and Humphries, {Martin J.} and Henggui Zhang and Pers, {Tune H.} and Olsen, {Jesper Velgaard} and Mark Boyett and Alicia Lundby",
year = "2019",
doi = "10.1038/s41467-019-10709-9",
language = "English",
volume = "10",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Springer Nature",
number = "1",

}

RIS

TY - JOUR

T1 - Quantitative proteomics and single-nucleus transcriptomics of the sinus node elucidates the foundation of cardiac pacemaking

AU - Linscheid, Nora

AU - Logantha, Sunil Jit R. J.

AU - Poulsen, Pi Camilla

AU - Zhang, Shanzhuo

AU - Schrölkamp, Maren

AU - Egerod, Kristoffer Lihme

AU - Thompson, Jonatan James

AU - Kitmitto, Ashraf

AU - Galli, Gina

AU - Humphries, Martin J.

AU - Zhang, Henggui

AU - Pers, Tune H.

AU - Olsen, Jesper Velgaard

AU - Boyett, Mark

AU - Lundby, Alicia

PY - 2019

Y1 - 2019

N2 - The sinus node is a collection of highly specialised cells constituting the heart’s pacemaker. The molecular underpinnings of its pacemaking abilities are debated. By high-resolution mass spectrometry, we quantify >7,000 proteins from sinus node and neighbouring atrial muscle. Abundances of 575 proteins differ between the two tissues. By performing single-nucleus RNA sequencing of sinus node biopsies, we attribute measured protein abundances to specific cell types. The data reveals significant differences in ion channels responsible for the membrane clock, but not in Ca2+ clock proteins, suggesting that the membrane clock underpins pacemaking. Consistently, incorporation of ion channel expression differences into a biophysically-detailed atrial action potential model result 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 cardiac pacemaker.

AB - The sinus node is a collection of highly specialised cells constituting the heart’s pacemaker. The molecular underpinnings of its pacemaking abilities are debated. By high-resolution mass spectrometry, we quantify >7,000 proteins from sinus node and neighbouring atrial muscle. Abundances of 575 proteins differ between the two tissues. By performing single-nucleus RNA sequencing of sinus node biopsies, we attribute measured protein abundances to specific cell types. The data reveals significant differences in ion channels responsible for the membrane clock, but not in Ca2+ clock proteins, suggesting that the membrane clock underpins pacemaking. Consistently, incorporation of ion channel expression differences into a biophysically-detailed atrial action potential model result 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 cardiac pacemaker.

U2 - 10.1038/s41467-019-10709-9

DO - 10.1038/s41467-019-10709-9

M3 - Article

VL - 10

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

IS - 1

ER -