ArticleNature2015
Hypoxia fate mapping identifies cycling cardiomyocytes in the adult heart.
Article in Nature, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to trial NCT05632432 (Autologous Atrial Appendage Micrografts Transplanted During Coronary Artery Bypass Surgery), which is not on this map. Cited by 200 papers, 2 of them syntheses that pooled 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.
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.
Autologous Atrial Appendage Micrografts Transplanted During Coronary Artery Bypass Surgery: the AAMS2 Randomized, Double-blinded, and Placebo-controlled Trial
Who cites it
200 citing papers in PubMed, 2 syntheses or guidelines pooled it, 314 citations in OpenAlex.
- Cardiac Regeneration: New Insights Into the Frontier of Ischemic Heart Failure Therapy.Frontiers in bioengineering and biotechnology · 2020Pooled it
- ESC Working Group on Cellular Biology of the Heart: position paper for Cardiovascular Research: tissue engineering strategies combined with cell therapies for cardiac repair in ischaemic heart disease and heart failure.Cardiovascular research · 2019Guideline
- Oxygen physiology and mechanisms of oxygen toxicity: a narrative review.Medical gas research · 2026Review
- Materialogenetics: an emerging and promising framework for cell-specific genetic manipulation.Bioactive materials · 2026Article
- Maternal Exercise and Offspring Cardiac Regenerative Potential: Roles of Apelin and α-Ketoglutarate.Biology · 2026Review
- Signaling pathways regulating cardiac regeneration.Cell regeneration (London, England) · 2026Review
- Cardiac regeneration and repair: the emerging mechanisms and therapeutic approaches.Molecular biomedicine · 2026Review
- Epigenetic Control of Mammalian Cardiomyocyte Proliferation.Current cardiology reports · 2026Review
- Hypoxia-mediated epicardial signaling coordinates coronary angiogenesis and myocardial expansion during zebrafish ventricle maturation.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Rejuvenating the damaged and aged heart: lessons from development.npj biomedical innovations · 2026Review
- Past, Present and Future of Regenerative Gene Therapy for Ischemic Heart Failure.Journal of cardiovascular translational research · 2026Review
- Cell-free strategies for cardiomyocyte proliferation and heart repair.Pharmacological reports : PR · 2026Review
- A modular tissue-clearing framework integrated with light-field microscopy enables rapid volumetric phenotyping of cardiac tissue.Research square · 2026Article
- Article
- LAP2 Isoform Profile in Heart Ageing and in Cardiac Cell Proliferation and Differentiation: Input From CRISPR-Cas9-mediated LAP2a Knockdown in H9C2.International journal of medical sciences · 2026Article
- Molecular gatekeepers of endogenous adult mammalian cardiomyocyte proliferation.Nature reviews. Cardiology · 2025Review
- Pluripotent stem cell-based approaches for heart repair and the potential of genetic modifications.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Hypoxia and Tissue Regeneration: Adaptive Mechanisms and Therapeutic Opportunities.International journal of molecular sciences · 2025Review
- Knockout of thyroid hormone receptor alpha a (thraa) enhances cardiac regeneration in zebrafish through metabolic and hypoxic regulation.Cell communication and signaling : CCS · 2025Article
- Article
140 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
- Erratum issued
Authors and funding
18 authors at 2 institutions in 2 countries.
Funding
Abstract
Although the adult mammalian heart is incapable of meaningful functional recovery following substantial cardiomyocyte loss, it is now clear that modest cardiomyocyte turnover occurs in adult mouse and human hearts, mediated primarily by proliferation of pre-existing cardiomyocytes. However, fate mapping of these cycling cardiomyocytes has not been possible thus far owing to the lack of identifiable genetic markers. In several organs, stem or progenitor cells reside in relatively hypoxic microenvironments where the stabilization of the hypoxia-inducible factor 1 alpha (Hif-1α) subunit is critical for their maintenance and function. Here we report fate mapping of hypoxic cells and their progenies by generating a transgenic mouse expressing a chimaeric protein in which the oxygen-dependent degradation (ODD) domain of Hif-1α is fused to the tamoxifen-inducible CreERT2 recombinase. In mice bearing the creERT2-ODD transgene driven by either the ubiquitous CAG promoter or the cardiomyocyte-specific α myosin heavy chain promoter, we identify a rare population of hypoxic cardiomyocytes that display characteristics of proliferative neonatal cardiomyocytes, such as smaller size, mononucleation and lower oxidative DNA damage. Notably, these hypoxic cardiomyocytes contributed widely to new cardiomyocyte formation in the adult heart. These results indicate that hypoxia signalling is an important hallmark of cycling cardiomyocytes, and suggest that hypoxia fate mapping can be a powerful tool for identifying cycling cells in adult mammals.
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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.