ArticleInternational journal of molecular sciences2017
Single-Construct Polycistronic Doxycycline-Inducible Vectors Improve Direct Cardiac Reprogramming and Can Be Used to Identify the Critical Timing of Transgene Expression.
Article in International journal of molecular sciences, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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Who cites it
16 citing papers in PubMed, 1 synthesis or guideline pooled it, 22 citations in OpenAlex.
- Cardiac Regeneration: New Insights Into the Frontier of Ischemic Heart Failure Therapy.Frontiers in bioengineering and biotechnology · 2020Pooled it
- Advances in fibroblast-based cardiac reprogramming in the treatment of heart disease.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025Review
- Termination sequence between an inducible promoter and ubiquitous chromatin opening element (UCOE) reduces gene expression leakage and silencing.Journal of biological engineering · 2025Article
- Fibroblast fate determination during cardiac reprogramming by remodeling of actin filaments.Stem cell reports · 2022Article
- Direct reprogramming as a route to cardiac repair.Seminars in cell & developmental biology · 2022Review
- Review
- Establishment of human airway epithelial cells with doxycycline-inducible cell growth and fluorescence reporters.Cytotechnology · 2021Article
- The Future of Direct Cardiac Reprogramming: AnyInternational journal of molecular sciences · 2020Review
- Assessing Cardiac Reprogramming using High Content Imaging Analysis.Journal of visualized experiments : JoVE · 2020Article
- Article
- Stoichiometric optimization of Gata4, Hand2, Mef2c, and Tbx5 expression for contractile cardiomyocyte reprogramming.Scientific reports · 2019Article
- Chemical suppression of specific C-C chemokine signaling pathways enhances cardiac reprogramming.The Journal of biological chemistry · 2019Article
- Direct Cardiac Reprogramming: A Novel Approach for Heart Regeneration.International journal of molecular sciences · 2018Review
- Chemical compound-based direct reprogramming for future clinical applications.Bioscience reports · 2018Review
- Direct Reprograming to Regenerate Myocardium and Repair Its Pacemaker and Conduction System.Medicines (Basel, Switzerland) · 2018Review
- Direct Cardiac Reprogramming: Progress and Promise.Stem cells international · 2018Review
Corrections and comments
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Authors and funding
15 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Direct reprogramming is a promising approach in regenerative medicine. Overexpression of the cardiac transcription factors Gata4, Mef2c, and Tbx5 (GMT) or GMT plus Hand2 (GHMT) directly reprogram fibroblasts into cardiomyocyte-like cells (iCMs). However, the critical timing of transgene expression and the molecular mechanisms for cardiac reprogramming remain unclear. The conventional doxycycline (Dox)-inducible temporal transgene expression systems require simultaneous transduction of two vectors (pLVX-rtTA/pLVX-cDNA) harboring the reverse tetracycline transactivator (rtTA) and the tetracycline response element (TRE)-controlled transgene, respectively, leading to inefficient cardiac reprogramming. Herein, we developed a single-construct-based polycistronic Dox-inducible vector (pDox-cDNA) expressing both the rtTA and TRE-controlled transgenes. Fluorescence activated cell sorting (FACS) analyses, quantitative RT-PCR, and immunostaining revealed that pDox-GMT increased cardiac reprogramming three-fold compared to the conventional pLVX-rtTA/pLVX-GMT. After four weeks, pDox-GMT-induced iCMs expressed multiple cardiac genes, produced sarcomeric structures, and beat spontaneously. Co-transduction of pDox-Hand2 with retroviral pMX-GMT increased cardiac reprogramming three-fold compared to pMX-GMT alone. Temporal Dox administration revealed that Hand2 transgene expression is critical during the first two weeks of cardiac reprogramming. Microarray analyses demonstrated that Hand2 represses cell cycle-promoting genes and enhances cardiac reprogramming. Thus, we have developed an efficient temporal transgene expression system, which could be invaluable in the study of cardiac reprogramming.
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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.