Evidence map›Paper›PMID 34349150›Full record

ArticleScientific reports2021

A comprehensive analysis of gene expression changes in a high replicate and open-source dataset of differentiating hiPSC-derived cardiomyocytes.

Tanya Grancharova, Kaytlyn A Gerbin, Alexander B Rosenberg, Charles M Roco, Joy E Arakaki, Colette M DeLizo, Stephanie Q Dinh, Rory M Donovan-Maiye, Matthew Hirano, Angelique M Nelson and 7 more

Abstract read
In one paragraph

Article in Scientific reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
40citing papers in PubMed, 1 pooled it
–field-weighted citation impact
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

40 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Review
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  4. Article
  5. Machine Learning in Stem Cell Research: From Biological Data to Clinical Translation.Computational and structural biotechnology journal · 2026
    Review
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  7. Article
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  17. Short-Term Electrical Stimulation Impacts Cardiac Cell Structure and Function.Journal of tissue engineering and regenerative medicine · 2025
    Article
  18. Article
  19. Cells · 2024
    Article
  20. Article
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

17 authors.

Tanya Grancharova *Allen Institute for Cell Science, Seattle, WA, USA.
Kaytlyn A Gerbin *Allen Institute for Cell Science, Seattle, WA, USA.
Alexander B RosenbergDepartment of Electrical & Computer Engineering, University of Washington, Seattle, WA, USA.
Charles M Roco, Parse Biosciences, Seattle, WA, USA.
Joy E ArakakiAllen Institute for Cell Science, Seattle, WA, USA.
Colette M DeLizoAllen Institute for Cell Science, Seattle, WA, USA.
Stephanie Q DinhAllen Institute for Cell Science, Seattle, WA, USA.
Rory M Donovan-MaiyeAllen Institute for Cell Science, Seattle, WA, USA.
Matthew HiranoDepartment of Electrical & Computer Engineering, University of Washington, Seattle, WA, USA.
Angelique M NelsonAllen Institute for Cell Science, Seattle, WA, USA.
Joyce TangAllen Institute for Cell Science, Seattle, WA, USA.
Julie A TheriotAllen Institute for Cell Science, Seattle, WA, USA.
Calysta YanAllen Institute for Cell Science, Seattle, WA, USA.
Vilas MenonDepartment of Neurology, Columbia University Irving Medical Center, New York, NY, USA.
Sean P PalecekDepartment of Chemical and Biological Engineering, University of Wisconsin - Madison, Madison, WI, USA.
Georg SeeligDepartment of Electrical & Computer Engineering, University of Washington, Seattle, WA, USA.
Ruwanthi N GunawardaneAllen Institute for Cell Science, Seattle, WA, USA. rug@alleninstitute.org.

Funding

High-resolution spatial transcriptomics through light patterningR21CA246358 · NCI · UNIVERSITY OF WASHINGTON · PI SEELIG, GEORG, WU, DAVID · 2020 to 2022
$578k
NCI NIH HHS R21 CA246358
6 · The paper itself

Abstract

We performed a comprehensive analysis of the transcriptional changes occurring during human induced pluripotent stem cell (hiPSC) differentiation to cardiomyocytes. Using single cell RNA-seq, we sequenced > 20,000 single cells from 55 independent samples representing two differentiation protocols and multiple hiPSC lines. Samples included experimental replicates ranging from undifferentiated hiPSCs to mixed populations of cells at D90 post-differentiation. Differentiated cell populations clustered by time point, with differential expression analysis revealing markers of cardiomyocyte differentiation and maturation changing from D12 to D90. We next performed a complementary cluster-independent sparse regression analysis to identify and rank genes that best assigned cells to differentiation time points. The two highest ranked genes between D12 and D24 (MYH7 and MYH6) resulted in an accuracy of 0.84, and the three highest ranked genes between D24 and D90 (A2M, H19, IGF2) resulted in an accuracy of 0.94, revealing that low dimensional gene features can identify differentiation or maturation stages in differentiating cardiomyocytes. Expression levels of select genes were validated using RNA FISH. Finally, we interrogated differences in cardiac gene expression resulting from two differentiation protocols, experimental replicates, and three hiPSC lines in the WTC-11 background to identify sources of variation across these experimental variables.

Indexed as

Cell DifferentiationGene Expression RegulationTranscriptomeBiomarkersHumansInduced Pluripotent Stem CellsMyocytes, CardiacRNA-SeqBiomarkers

Identifiers

PMID34349150
PMCPMC8338992

What OpenQuestion holds

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Registered trials

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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.