Evidence map›Paper›PMID 35359438›Full record

ArticleFrontiers in cell and developmental biology2022

Sympathetic Neurons Regulate Cardiomyocyte Maturation in Culture.

William J Kowalski, Iris H Garcia-Pak, Wenling Li, Hideki Uosaki, Emmanouil Tampakakis, Jizhong Zou, Yongshun Lin, Kira Patterson, Chulan Kwon, Yoh-Suke Mukouyama

Open access · goldAbstract read
In one paragraph

Article in Frontiers in cell and developmental biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed, 1 pooled it
5.6field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

24 citing papers in PubMed, 1 synthesis or guideline pooled it, 37 citations in OpenAlex.

  1. Pooled it
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  13. Advancing organ-on-chip systems: the role of microfluidics in neuro-cardiac research.Current research in pharmacology and drug discovery · 2025
    Review
  14. Article
  15. Article
  16. Article
  17. Cardiac maturation.Journal of molecular and cellular cardiology · 2024
    Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 4 institutions in 2 countries.

William J KowalskiLaboratory of Stem Cell and Neuro-Vascular Biology, Cell and Developmental Biology Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, United States.
Iris H Garcia-PakLaboratory of Stem Cell and Neuro-Vascular Biology, Cell and Developmental Biology Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, United States.
Wenling LiLaboratory of Stem Cell and Neuro-Vascular Biology, Cell and Developmental Biology Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, United States.
Hideki UosakiDivision of Cardiology, Department of Medicine, Johns Hopkins University, Baltimore, MD, United States.
Emmanouil TampakakisDivision of Cardiology, Department of Medicine, Johns Hopkins University, Baltimore, MD, United States.
Jizhong ZouIPSC Core Facility, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, United States.
Yongshun LinIPSC Core Facility, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, United States.
Kira PattersonIPSC Core Facility, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, United States.
Chulan KwonDivision of Cardiology, Department of Medicine, Johns Hopkins University, Baltimore, MD, United States.
Yoh-Suke MukouyamaLaboratory of Stem Cell and Neuro-Vascular Biology, Cell and Developmental Biology Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, United States.
National Institutes of Health · USNational Heart Lung and Blood Institute · USJohns Hopkins University · USJichi Medical University · JP

Funding

NHLBI iPSC Core FacilityZICHL006145 · NHLBI · NATIONAL HEART, LUNG, AND BLOOD INSTITUTE · PI ZOU, JIZHONG · 2012 to 2025
$23.3M
The study of neuro-vascular interactions in the developing heartZIAHL006116 · NHLBI · NATIONAL HEART, LUNG, AND BLOOD INSTITUTE · PI MUKOUYAMA, YOH-SUKE · 2011 to 2025
$9.4M
Microphysiological Model of Human Cardiac Sympathetic InnervationR01HL164936 · NHLBI · JOHNS HOPKINS UNIVERSITY · PI KIM, DEOK-HO, KWON, CHULAN · 2022 to 2025
$3.2M
Engineering a power switch to study the contribution of stem cell-derived cardiomyocytes on heart regenerationK08HL145135 · NHLBI · JOHNS HOPKINS UNIVERSITY · PI TAMPAKAKIS, EMMANOUIL · 2019 to 2023
$859k
NHLBI NIH HHS K08 HL145135NHLBI NIH HHS R01 HL164936
6 · The paper itself

Abstract

Embryos devoid of autonomic innervation suffer sudden cardiac death. However, whether autonomic neurons have a role in heart development is poorly understood. To investigate if sympathetic neurons impact cardiomyocyte maturation, we co-cultured phenotypically immature cardiomyocytes derived from human induced pluripotent stem cells with mouse sympathetic ganglion neurons. We found that 1) multiple cardiac structure and ion channel genes related to cardiomyocyte maturation were up-regulated when co-cultured with sympathetic neurons; 2) sarcomere organization and connexin-43 gap junctions increased; 3) calcium imaging showed greater transient amplitudes. However, sarcomere spacing, relaxation time, and level of sarcoplasmic reticulum calcium did not show matured phenotypes. We further found that addition of endothelial and epicardial support cells did not enhance maturation to a greater extent beyond sympathetic neurons, while administration of isoproterenol alone was insufficient to induce changes in gene expression. These results demonstrate that sympathetic neurons have a significant and complex role in regulating cardiomyocyte development.

Indexed as

cardiomyocyte maturationco-cultureheart developmentiPS cellssympathetic innervation

Identifiers

PMID35359438
PMCPMC8961983
OpenAlexW4220844495

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.