Evidence map›Paper›PMID 29531836›Full record

ArticleCell death discovery2018

Mitochondrial fission protein Drp1 inhibition promotes cardiac mesodermal differentiation of human pluripotent stem cells.

Ashfaqul Hoque, Priyadharshini Sivakumaran, Simon T Bond, Naomi X Y Ling, Anne M Kong, John W Scott, Nadeeka Bandara, Damián Hernández, Guei-Sheung Liu, Raymond C B Wong and 7 more

Open access · goldAbstract read
In one paragraph

Article in Cell death discovery, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.

0numbers the graph read from it
0cells of the map it votes in
51citing papers in PubMed
4.2field-weighted citation impact, top 5% 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

51 citing papers in PubMed, 89 citations in OpenAlex.

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  19. Maternal Inflammation During Pregnancy and Offspring Brain Development: The Role of Mitochondria.Biological psychiatry. Cognitive neuroscience and neuroimaging · 2022
    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

17 authors at 7 institutions in 4 countries.

Ashfaqul Hoque *1St Vincent's Institute of Medical Research, Fitzroy, VIC 3065 Australia.ORCID 0000-0003-2384-2983
Priyadharshini Sivakumaran *1St Vincent's Institute of Medical Research, Fitzroy, VIC 3065 Australia.
Simon T Bond *Molecular Metabolism and Ageing Laboratory, Baker Heart and Diabetes Institute, Melbourne, VIC 3004 Australia.
Naomi X Y Ling1St Vincent's Institute of Medical Research, Fitzroy, VIC 3065 Australia.
Anne M Kong1St Vincent's Institute of Medical Research, Fitzroy, VIC 3065 Australia.
John W Scott1St Vincent's Institute of Medical Research, Fitzroy, VIC 3065 Australia.
Nadeeka Bandara1St Vincent's Institute of Medical Research, Fitzroy, VIC 3065 Australia.
Damián Hernández4Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, East Melbourne, VIC 3065 Australia.
Guei-Sheung Liu4Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, East Melbourne, VIC 3065 Australia.
Raymond C B Wong4Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, East Melbourne, VIC 3065 Australia.
Michael T Ryan8Department of Biochemistry and Molecular Biology, Monash Biomedicine Discovery Institute, Monash University, Melbourne, VIC 3800 Australia.ORCID 0000-0003-2586-8829
Derek J Hausenloy9Hatter Cardiovascular Institute, University College London, London, WC1E 6HX UK.
Bruce E Kemp1St Vincent's Institute of Medical Research, Fitzroy, VIC 3065 Australia.
Jonathan S Oakhill1St Vincent's Institute of Medical Research, Fitzroy, VIC 3065 Australia.
Brian G DrewMolecular Metabolism and Ageing Laboratory, Baker Heart and Diabetes Institute, Melbourne, VIC 3004 Australia.
Alice Pébay4Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, East Melbourne, VIC 3065 Australia.
Shiang Y Lim1St Vincent's Institute of Medical Research, Fitzroy, VIC 3065 Australia.
St Vincents Institute of Medical Research · AUThe University of Melbourne · AUBaker Heart and Diabetes Institute · AUCharles Sturt University · AUDiscovery Institute · USSt Bartholomew's Hospital · GBUniversity of Tasmania · AU

Funding

British Heart Foundation FS/10/39/28270British Heart Foundation FS/13/41/30368Medical Research Council MR/J003530/1
6 · The paper itself

Abstract

Human induced pluripotent stem cells (iPSCs) are a valuable tool for studying the cardiac developmental process in vitro, and cardiomyocytes derived from iPSCs are a putative cell source for personalized medicine. Changes in mitochondrial morphology have been shown to occur during cellular reprogramming and pluripotent stem cell differentiation. However, the relationships between mitochondrial dynamics and cardiac mesoderm commitment of iPSCs remain unclear. Here we demonstrate that changes in mitochondrial morphology from a small granular fragmented phenotype in pluripotent stem cells to a filamentous reticular elongated network in differentiated cardiomyocytes are required for cardiac mesodermal differentiation. Genetic and pharmacological inhibition of the mitochondrial fission protein, Drp1, by either small interfering RNA or Mdivi-1, respectively, increased cardiac mesoderm gene expression in iPSCs. Treatment of iPSCs with Mdivi-1 during embryoid body formation significantly increased the percentage of beating embryoid bodies and expression of cardiac-specific genes. Furthermore, Drp1 gene silencing was accompanied by increased mitochondrial respiration and decreased aerobic glycolysis. Our findings demonstrate that shifting the balance of mitochondrial morphology toward fusion by inhibition of Drp1 promoted cardiac differentiation of human iPSCs with a metabolic shift from glycolysis towards oxidative phosphorylation. These findings suggest that Drp1 may represent a new molecular target for future development of strategies to promote the differentiation of human iPSCs into cardiac lineages for patient-specific cardiac regenerative medicine.

Identifiers

PMID29531836
PMCPMC5841367
OpenAlexW2806136689

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.