↓ Skip to main content

Subtype-specific differentiation of cardiac pacemaker cell clusters from human induced pluripotent stem cells

Overview of attention for article published in Stem Cell Research & Therapy, October 2017
Altmetric Badge

About this Attention Score

  • In the top 25% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (89th percentile)
  • High Attention Score compared to outputs of the same age and source (96th percentile)

Mentioned by

news
1 news outlet
blogs
1 blog
twitter
3 tweeters
wikipedia
1 Wikipedia page

Citations

dimensions_citation
35 Dimensions

Readers on

mendeley
79 Mendeley
You are seeing a free-to-access but limited selection of the activity Altmetric has collected about this research output. Click here to find out more.
Title
Subtype-specific differentiation of cardiac pacemaker cell clusters from human induced pluripotent stem cells
Published in
Stem Cell Research & Therapy, October 2017
DOI 10.1186/s13287-017-0681-4
Pubmed ID
Authors

Patrick A. Schweizer, Fabrice F. Darche, Nina D. Ullrich, Pascal Geschwill, Boris Greber, Rasmus Rivinius, Claudia Seyler, Karin Müller-Decker, Andreas Draguhn, Jochen Utikal, Michael Koenen, Hugo A. Katus, Dierk Thomas

Abstract

Human induced pluripotent stem cells (hiPSC) harbor the potential to differentiate into diverse cardiac cell types. Previous experimental efforts were primarily directed at the generation of hiPSC-derived cells with ventricular cardiomyocyte characteristics. Aiming at a straightforward approach for pacemaker cell modeling and replacement, we sought to selectively differentiate cells with nodal-type properties. hiPSC were differentiated into spontaneously beating clusters by co-culturing with visceral endoderm-like cells in a serum-free medium. Subsequent culturing in a specified fetal bovine serum (FBS)-enriched cell medium produced a pacemaker-type phenotype that was studied in detail using quantitative real-time polymerase chain reaction (qRT-PCR), immunocytochemistry, and patch-clamp electrophysiology. Further investigations comprised pharmacological stimulations and co-culturing with neonatal cardiomyocytes. hiPSC co-cultured in a serum-free medium with the visceral endoderm-like cell line END-2 produced spontaneously beating clusters after 10-12 days of culture. The pacemaker-specific genes HCN4, TBX3, and TBX18 were abundantly expressed at this early developmental stage, while levels of sarcomeric gene products remained low. We observed that working-type cardiomyogenic differentiation can be suppressed by transfer of early clusters into a FBS-enriched cell medium immediately after beating onset. After 6 weeks under these conditions, sinoatrial node (SAN) hallmark genes remained at high levels, while working-type myocardial transcripts (NKX2.5, TBX5) were low. Clusters were characterized by regular activity and robust beating rates (70-90 beats/min) and were triggered by spontaneous Ca(2+) transients recapitulating calcium clock properties of genuine pacemaker cells. They were responsive to adrenergic/cholinergic stimulation and able to pace neonatal rat ventricular myocytes in co-culture experiments. Action potential (AP) measurements of cells individualized from clusters exhibited nodal-type (63.4%) and atrial-type (36.6%) AP morphologies, while ventricular AP configurations were not observed. We provide a novel culture media-based, transgene-free approach for targeted generation of hiPSC-derived pacemaker-type cells that grow in clusters and offer the potential for disease modeling, drug testing, and individualized cell-based replacement therapy of the SAN.

Twitter Demographics

The data shown below were collected from the profiles of 3 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 79 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 79 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 17 22%
Researcher 15 19%
Student > Master 13 16%
Student > Bachelor 7 9%
Other 4 5%
Other 9 11%
Unknown 14 18%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 22 28%
Agricultural and Biological Sciences 16 20%
Medicine and Dentistry 8 10%
Engineering 4 5%
Chemistry 2 3%
Other 5 6%
Unknown 22 28%

Attention Score in Context

This research output has an Altmetric Attention Score of 21. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 28 August 2020.
All research outputs
#1,378,463
of 20,881,490 outputs
Outputs from Stem Cell Research & Therapy
#67
of 2,142 outputs
Outputs of similar age
#35,864
of 342,243 outputs
Outputs of similar age from Stem Cell Research & Therapy
#7
of 194 outputs
Altmetric has tracked 20,881,490 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 93rd percentile: it's in the top 10% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 2,142 research outputs from this source. They receive a mean Attention Score of 4.9. This one has done particularly well, scoring higher than 96% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 342,243 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 89% of its contemporaries.
We're also able to compare this research output to 194 others from the same source and published within six weeks on either side of this one. This one has done particularly well, scoring higher than 96% of its contemporaries.