Evidence map›Paper›PMID 34404774›Full record

ArticleNature communications2021

Human iPS-derived pre-epicardial cells direct cardiomyocyte aggregation expansion and organization in vitro.

Jun Jie Tan, Jacques P Guyette, Kenji Miki, Ling Xiao, Gurbani Kaur, Tong Wu, Liye Zhu, Katrina J Hansen, King-Hwa Ling, David J Milan and 1 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.

0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed
3.4field-weighted citation impact, top 6% 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

36 citing papers in PubMed, 53 citations in OpenAlex.

  1. Retinoic acid in health and disease.Signal transduction and targeted therapy · 2026
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  5. Coordination of cardiogenesis in vivo and in vitro.Nature reviews. Molecular cell biology · 2026
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  7. B cells promote atrial fibrillation via autoantibodies.Nature cardiovascular research · 2025
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  15. The molecular mechanisms of cardiac development and related diseases.Signal transduction and targeted therapy · 2024
    Review
  16. Article
  17. Article
  18. Article
  19. 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

11 authors at 4 institutions in 3 countries.

Jun Jie Tan *Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA, USA. jjtan@usm.my.
Jacques P Guyette *Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA, USA.
Kenji MikiCenter for Regenerative Medicine, Massachusetts General Hospital, Boston, MA, USA.ORCID 0000-0001-7901-6133
Ling XiaoHarvard Medical School, Boston, MA, USA.ORCID 0000-0002-5463-5576
Gurbani KaurCenter for Regenerative Medicine, Massachusetts General Hospital, Boston, MA, USA.ORCID 0000-0003-3822-9911
Tong WuCenter for Regenerative Medicine, Massachusetts General Hospital, Boston, MA, USA.
Liye ZhuCenter for Regenerative Medicine, Massachusetts General Hospital, Boston, MA, USA.
Katrina J HansenWorcester Polytechnic Institute, Dept. of Biomedical Engineering, Worcester, MA, USA.
King-Hwa LingDepartment of Genetics, Harvard Medical School, Boston, MA, USA.ORCID 0000-0002-3968-7263
David J MilanHarvard Medical School, Boston, MA, USA.
Harald C OttCenter for Regenerative Medicine, Massachusetts General Hospital, Boston, MA, USA. hott@mgh.harvard.edu.ORCID 0000-0003-0843-9934
Harvard University · USMassachusetts General Hospital · USUniversiti Putra Malaysia · MYWorcester Polytechnic Institute · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Epicardial formation is necessary for normal myocardial morphogenesis. Here, we show that differentiating hiPSC-derived lateral plate mesoderm with BMP4, RA and VEGF (BVR) can generate a premature form of epicardial cells (termed pre-epicardial cells, PECs) expressing WT1, TBX18, SEMA3D, and SCX within 7 days. BVR stimulation after Wnt inhibition of LPM demonstrates co-differentiation and spatial organization of PECs and cardiomyocytes (CMs) in a single 2D culture. Co-culture consolidates CMs into dense aggregates, which then form a connected beating syncytium with enhanced contractility and calcium handling; while PECs become more mature with significant upregulation of UPK1B, ITGA4, and ALDH1A2 expressions. Our study also demonstrates that PECs secrete IGF2 and stimulate CM proliferation in co-culture. Three-dimensional PEC-CM spheroid co-cultures form outer smooth muscle cell layers on cardiac micro-tissues with organized internal luminal structures. These characteristics suggest PECs could play a key role in enhancing tissue organization within engineered cardiac constructs in vitro.

Indexed as

Coculture TechniquesAldehyde Dehydrogenase 1 FamilyBasic Helix-Loop-Helix ProteinsBone Morphogenetic Protein 4CalciumCell AggregationCell DifferentiationGenes, Wilms TumorHumansInduced Pluripotent Stem CellsInsulin-Like Growth Factor IIMesodermMyocytes, CardiacMyocytes, Smooth MuscleRetinal DehydrogenaseSemaphorinsAldehyde Dehydrogenase 1 FamilyALDH1A2 protein, humanBasic Helix-Loop-Helix ProteinsBMP4 protein, humanBone Morphogenetic Protein 4CalciumIGF2 protein, humanInsulin-Like Growth Factor IIRetinal DehydrogenaseSCX protein, humanSema3D protein, humanSemaphorinsT-Box Domain ProteinsTbx18 protein, human

Identifiers

PMID34404774
PMCPMC8370973
OpenAlexW3193779575

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.