Further insights into the molecular complexity of the human sinus node - The role of 'novel' transcription factors and microRNAsCitation formats

  • External authors:
  • Abimbola J Aminu
  • Maria Petkova
  • Joseph Yanni
  • Alex D Morris
  • Robert T Simms
  • Weixuan Chen
  • Marcin Kuniewicz
  • Mateusz K Holda
  • Vladislav S Kuzmin
  • Filip Perde
  • Peter Molenaar

Standard

Further insights into the molecular complexity of the human sinus node - The role of 'novel' transcription factors and microRNAs. / Aminu, Abimbola J; Petkova, Maria; Atkinson, Andrew J; Yanni, Joseph; Morris, Alex D; Simms, Robert T; Chen, Weixuan; Yin, Zeyuan; Kuniewicz, Marcin; Holda, Mateusz K; Kuzmin, Vladislav S; Perde, Filip; Molenaar, Peter; Dobrzynski, Halina.

In: Progress in biophysics and molecular biology, Vol. 166, 01.11.2021, p. 86-104.

Research output: Contribution to journalArticlepeer-review

Harvard

Aminu, AJ, Petkova, M, Atkinson, AJ, Yanni, J, Morris, AD, Simms, RT, Chen, W, Yin, Z, Kuniewicz, M, Holda, MK, Kuzmin, VS, Perde, F, Molenaar, P & Dobrzynski, H 2021, 'Further insights into the molecular complexity of the human sinus node - The role of 'novel' transcription factors and microRNAs', Progress in biophysics and molecular biology, vol. 166, pp. 86-104. https://doi.org/10.1016/j.pbiomolbio.2021.04.008

APA

Aminu, A. J., Petkova, M., Atkinson, A. J., Yanni, J., Morris, A. D., Simms, R. T., Chen, W., Yin, Z., Kuniewicz, M., Holda, M. K., Kuzmin, V. S., Perde, F., Molenaar, P., & Dobrzynski, H. (2021). Further insights into the molecular complexity of the human sinus node - The role of 'novel' transcription factors and microRNAs. Progress in biophysics and molecular biology, 166, 86-104. https://doi.org/10.1016/j.pbiomolbio.2021.04.008

Vancouver

Aminu AJ, Petkova M, Atkinson AJ, Yanni J, Morris AD, Simms RT et al. Further insights into the molecular complexity of the human sinus node - The role of 'novel' transcription factors and microRNAs. Progress in biophysics and molecular biology. 2021 Nov 1;166:86-104. https://doi.org/10.1016/j.pbiomolbio.2021.04.008

Author

Aminu, Abimbola J ; Petkova, Maria ; Atkinson, Andrew J ; Yanni, Joseph ; Morris, Alex D ; Simms, Robert T ; Chen, Weixuan ; Yin, Zeyuan ; Kuniewicz, Marcin ; Holda, Mateusz K ; Kuzmin, Vladislav S ; Perde, Filip ; Molenaar, Peter ; Dobrzynski, Halina. / Further insights into the molecular complexity of the human sinus node - The role of 'novel' transcription factors and microRNAs. In: Progress in biophysics and molecular biology. 2021 ; Vol. 166. pp. 86-104.

Bibtex

@article{9b47dd5fe83a49c3a34cd97824c1ac0f,
title = "Further insights into the molecular complexity of the human sinus node - The role of 'novel' transcription factors and microRNAs",
abstract = "RESEARCH PURPOSE: The sinus node (SN) is the heart's primary pacemaker. Key ion channels (mainly the funny channel, HCN4) and Ca2+-handling proteins in the SN are responsible for its function. Transcription factors (TFs) regulate gene expression through inhibition or activation and microRNAs (miRs) do this through inhibition. There is high expression of macrophages and mast cells within the SN connective tissue. 'Novel'/unexplored TFs and miRs in the regulation of ion channels and immune cells in the SN are not well understood. Using RNAseq and bioinformatics, the expression profile and predicted interaction of key TFs and cell markers with key miRs in the adult human SN vs. right atrial tissue (RA) were determined.PRINCIPAL RESULTS: 68 and 60 TFs significantly more or less expressed in the SN vs. RA respectively. Among those more expressed were ISL1 and TBX3 (involved in embryonic development of the SN) and 'novel' RUNX1-2, CEBPA, GLI1-2 and SOX2. These TFs were predicted to regulate HCN4 expression in the SN. Markers for different cells: fibroblasts (COL1A1), fat (FABP4), macrophages (CSF1R and CD209), natural killer (GZMA) and mast (TPSAB1) were significantly more expressed in the SN vs. RA. Interestingly, RUNX1-3, CEBPA and GLI1 also regulate expression of these cells. MiR-486-3p inhibits HCN4 and markers involved in immune response.MAJOR CONCLUSIONS: In conclusion, RUNX1-2, CSF1R, TPSAB1, COL1A1 and HCN4 are highly expressed in the SN but not miR-486-3p. Their complex interactions can be used to treat SN dysfunction such as bradycardia. Interestingly, another research group recently reported miR-486-3p is upregulated in blood samples from severe COVID-19 patients who suffer from bradycardia.",
keywords = "COVID-19, Humans, Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels/genetics, MicroRNAs/genetics, SARS-CoV-2, Sinoatrial Node, Transcription Factors/genetics",
author = "Aminu, {Abimbola J} and Maria Petkova and Atkinson, {Andrew J} and Joseph Yanni and Morris, {Alex D} and Simms, {Robert T} and Weixuan Chen and Zeyuan Yin and Marcin Kuniewicz and Holda, {Mateusz K} and Kuzmin, {Vladislav S} and Filip Perde and Peter Molenaar and Halina Dobrzynski",
note = "Copyright {\textcopyright} 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.",
year = "2021",
month = nov,
day = "1",
doi = "10.1016/j.pbiomolbio.2021.04.008",
language = "English",
volume = "166",
pages = "86--104",
journal = "Progress in biophysics and molecular biology",
issn = "0079-6107",
publisher = "Elsevier BV",

}

RIS

TY - JOUR

T1 - Further insights into the molecular complexity of the human sinus node - The role of 'novel' transcription factors and microRNAs

AU - Aminu, Abimbola J

AU - Petkova, Maria

AU - Atkinson, Andrew J

AU - Yanni, Joseph

AU - Morris, Alex D

AU - Simms, Robert T

AU - Chen, Weixuan

AU - Yin, Zeyuan

AU - Kuniewicz, Marcin

AU - Holda, Mateusz K

AU - Kuzmin, Vladislav S

AU - Perde, Filip

AU - Molenaar, Peter

AU - Dobrzynski, Halina

N1 - Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.

PY - 2021/11/1

Y1 - 2021/11/1

N2 - RESEARCH PURPOSE: The sinus node (SN) is the heart's primary pacemaker. Key ion channels (mainly the funny channel, HCN4) and Ca2+-handling proteins in the SN are responsible for its function. Transcription factors (TFs) regulate gene expression through inhibition or activation and microRNAs (miRs) do this through inhibition. There is high expression of macrophages and mast cells within the SN connective tissue. 'Novel'/unexplored TFs and miRs in the regulation of ion channels and immune cells in the SN are not well understood. Using RNAseq and bioinformatics, the expression profile and predicted interaction of key TFs and cell markers with key miRs in the adult human SN vs. right atrial tissue (RA) were determined.PRINCIPAL RESULTS: 68 and 60 TFs significantly more or less expressed in the SN vs. RA respectively. Among those more expressed were ISL1 and TBX3 (involved in embryonic development of the SN) and 'novel' RUNX1-2, CEBPA, GLI1-2 and SOX2. These TFs were predicted to regulate HCN4 expression in the SN. Markers for different cells: fibroblasts (COL1A1), fat (FABP4), macrophages (CSF1R and CD209), natural killer (GZMA) and mast (TPSAB1) were significantly more expressed in the SN vs. RA. Interestingly, RUNX1-3, CEBPA and GLI1 also regulate expression of these cells. MiR-486-3p inhibits HCN4 and markers involved in immune response.MAJOR CONCLUSIONS: In conclusion, RUNX1-2, CSF1R, TPSAB1, COL1A1 and HCN4 are highly expressed in the SN but not miR-486-3p. Their complex interactions can be used to treat SN dysfunction such as bradycardia. Interestingly, another research group recently reported miR-486-3p is upregulated in blood samples from severe COVID-19 patients who suffer from bradycardia.

AB - RESEARCH PURPOSE: The sinus node (SN) is the heart's primary pacemaker. Key ion channels (mainly the funny channel, HCN4) and Ca2+-handling proteins in the SN are responsible for its function. Transcription factors (TFs) regulate gene expression through inhibition or activation and microRNAs (miRs) do this through inhibition. There is high expression of macrophages and mast cells within the SN connective tissue. 'Novel'/unexplored TFs and miRs in the regulation of ion channels and immune cells in the SN are not well understood. Using RNAseq and bioinformatics, the expression profile and predicted interaction of key TFs and cell markers with key miRs in the adult human SN vs. right atrial tissue (RA) were determined.PRINCIPAL RESULTS: 68 and 60 TFs significantly more or less expressed in the SN vs. RA respectively. Among those more expressed were ISL1 and TBX3 (involved in embryonic development of the SN) and 'novel' RUNX1-2, CEBPA, GLI1-2 and SOX2. These TFs were predicted to regulate HCN4 expression in the SN. Markers for different cells: fibroblasts (COL1A1), fat (FABP4), macrophages (CSF1R and CD209), natural killer (GZMA) and mast (TPSAB1) were significantly more expressed in the SN vs. RA. Interestingly, RUNX1-3, CEBPA and GLI1 also regulate expression of these cells. MiR-486-3p inhibits HCN4 and markers involved in immune response.MAJOR CONCLUSIONS: In conclusion, RUNX1-2, CSF1R, TPSAB1, COL1A1 and HCN4 are highly expressed in the SN but not miR-486-3p. Their complex interactions can be used to treat SN dysfunction such as bradycardia. Interestingly, another research group recently reported miR-486-3p is upregulated in blood samples from severe COVID-19 patients who suffer from bradycardia.

KW - COVID-19

KW - Humans

KW - Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels/genetics

KW - MicroRNAs/genetics

KW - SARS-CoV-2

KW - Sinoatrial Node

KW - Transcription Factors/genetics

U2 - 10.1016/j.pbiomolbio.2021.04.008

DO - 10.1016/j.pbiomolbio.2021.04.008

M3 - Article

C2 - 34004232

VL - 166

SP - 86

EP - 104

JO - Progress in biophysics and molecular biology

JF - Progress in biophysics and molecular biology

SN - 0079-6107

ER -