ArticleJournal of the American College of Cardiology2015
Nucleostemin rejuvenates cardiac progenitor cells and antagonizes myocardial aging.
Article in Journal of the American College of Cardiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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.
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.
Who cites it
39 citing papers in PubMed, 71 citations in OpenAlex.
- Cellular senescence and cell therapy in cardiovascular diseases.Stem cell research & therapy · 2025Review
- Myocardial ischemia-reperfusion injury upregulates nucleostemin expression via HIF-1α and c-Jun pathways and alleviates apoptosis by promoting autophagy.Cell death discovery · 2024Article
- Scalable Generation of Nanovesicles from Human-Induced Pluripotent Stem Cells for Cardiac Repair.International journal of molecular sciences · 2022Article
- The role of cellular senescence in cardiac disease: basic biology and clinical relevance.Nature reviews. Cardiology · 2022Review
- Nucleolar stress: Friend or foe in cardiac function?Frontiers in cardiovascular medicine · 2022Review
- Coordination of endothelial cell positioning and fate specification by the epicardium.Nature communications · 2021Article
- Pim1 maintains telomere length in mouse cardiomyocytes by inhibiting TGFβ signalling.Cardiovascular research · 2021Article
- Opportunities and Challenges in Stem Cell Aging.Advances in experimental medicine and biology · 2021Review
- Enhancing myocardial repair with CardioClusters.Nature communications · 2020Article
- Extra-telomeric impact of telomeres: Emerging molecular connections in pluripotency or stemness.The Journal of biological chemistry · 2020Review
- Review
- Adaptation within embryonic and neonatal heart environment reveals alternative fates for adult c-kitStem cells translational medicine · 2020Article
- Human CardioChimeras: Creation of a Novel "Next-Generation" Cardiac Cell.Journal of the American Heart Association · 2020Article
- Safety profiling of genetically engineered Pim-1 kinase overexpression for oncogenicity risk in human c-kit+ cardiac interstitial cells.Gene therapy · 2019Article
- Adult Cardiac Stem Cell Aging: A Reversible Stochastic Phenomenon?Oxidative medicine and cellular longevity · 2019Review
- BIN1 Induces the Formation of T-Tubules and Adult-Like CaStem cells (Dayton, Ohio) · 2019Article
- Cardiac interstitial tetraploid cells can escape replicative senescence in rodents but not large mammals.Communications biology · 2019Article
- Cardiac ageing: extrinsic and intrinsic factors in cellular renewal and senescence.Nature reviews. Cardiology · 2018Review
- Short Telomeres Induce p53 and Autophagy and Modulate Age-Associated Changes in Cardiac Progenitor Cell Fate.Stem cells (Dayton, Ohio) · 2018Article
- Mechanisms of Cardiac Repair and Regeneration.Circulation research · 2018Review
Corrections and comments
- Commented on by
Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundFunctional decline in stem cell-mediated regeneration contributes to aging associated with cellular senescence in c-kit+ cardiac progenitor cells (CPCs). Clinical implementation of CPC-based therapy in elderly patients would benefit tremendously from understanding molecular characteristics of senescence to antagonize aging. Nucleostemin (NS) is a nucleolar protein regulating stem cell proliferation and pluripotency.
objectivesThis study sought to demonstrate that NS preserves characteristics associated with "stemness" in CPCs and antagonizes myocardial senescence and aging.
methodsCPCs isolated from human fetal (fetal human cardiac progenitor cell [FhCPC]) and adult failing (adult human cardiac progenitor cell [AhCPC]) hearts, as well as young (young cardiac progenitor cell [YCPC]) and old mice (old cardiac progenitor cell [OCPC]), were studied for senescence characteristics and NS expression. Heterozygous knockout mice with 1 functional allele of NS (NS+/-) were used to demonstrate that NS preserves myocardial structure and function and slows characteristics of aging.
resultsNS expression is decreased in AhCPCs relative to FhCPCs, correlating with lowered proliferation potential and shortened telomere length. AhCPC characteristics resemble those of OCPCs, which have a phenotype induced by NS silencing, resulting in cell flattening, senescence, multinucleated cells, decreased S-phase progression, diminished expression of stemness markers, and up-regulation of p53 and p16. CPC senescence resulting from NS loss is partially p53 dependent and is rescued by concurrent silencing of p53. Mechanistically, NS induction correlates with Pim-1 kinase-mediated stabilization of c-Myc. Engineering OCPCs and AhCPCs to overexpress NS decreases senescent and multinucleated cells, restores morphology, and antagonizes senescence, thereby preserving phenotypic properties of "stemness." Early cardiac aging with a decline in cardiac function, an increase in senescence markers p53 and p16, telomere attrition, and accompanied CPC exhaustion is evident in NS+/- mice.
conclusionsYouthful properties and antagonism of senescence in CPCs and the myocardium are consistent with a role for NS downstream from Pim-1 signaling that enhances cardiac regeneration.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.