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Alternative Cultures for Human Pluripotent Stem Cell Production, Maintenance, and Genetic Analysis
Published on: July 24, 2014
NORAD Overexpression Enhances hiPSC-CM Regenerative Potency via PUM2/MASTL Signaling.
Kanghui Huan1,2,3, Yujian Jiang2, Xin Xie1
1Department of Cardiology, Binzhou Medical University Hospital, Binzhou Medical University, China (K.H., X.X., Y.C., W.B.).
Arteriosclerosis, Thrombosis, and Vascular Biology
|June 25, 2026
Summary
Long noncoding RNA NORAD enhances human pluripotent stem cell-derived cardiomyocyte (hiPSC-CM) engraftment and cell-cycle activity for myocardial repair. NORAD promotes cell-cycle progression and cardiac function post-infarction, offering therapeutic potential.
Area of Science:
- Cardiovascular Biology
- Stem Cell Therapy
- Molecular Medicine
Background:
- Engraftment of human pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) for myocardial infarction therapy is limited by poor cell-cycle activity and survival.
- The long noncoding RNA NORAD (activated by DNA damage) is investigated for its potential to enhance hiPSC-CM function.
Purpose of the Study:
- To explore the role of NORAD in improving cell-cycle activity and engraftment of hiPSC-CMs.
- To investigate the underlying molecular mechanisms and therapeutic potential of NORAD in myocardial repair.
Main Methods:
- hiPSC-CMs were engineered to overexpress or knockdown NORAD.
- In vitro assays assessed cell-cycle activity, maturation, and apoptosis.
- A murine myocardial infarction model was used to evaluate transplanted hiPSC-CMs, assessing engraftment, cardiac function, and infarct size.
- Molecular mechanisms involving PUM2, MASTL, and exosome-mediated effects were investigated.
Main Results:
- NORAD overexpression significantly increased hiPSC-CM cell-cycle markers (Ki67, pH3, Aurora B, EdU) and diploid nuclei, while reducing apoptosis.
- Transplantation of NORAD-overexpressing hiPSC-CMs improved myocardial repair, enhancing cell-cycle activity in engrafted and endogenous cells.
- NORAD was found to sequester PUM2, relieving translational repression of MASTL, a key mitotic regulator.
- Exosomes from NORAD-overexpressing hiPSC-CMs promoted recipient cardiomyocyte cell-cycle activity.
Conclusions:
- NORAD promotes hiPSC-CM cell-cycle progression through the PUM2/MASTL axis.
- Exosomes derived from NORAD-modified hiPSC-CMs contribute to myocardial repair by stimulating endogenous cardiomyocyte proliferation.
- NORAD-modulated hiPSC-CMs demonstrate significant therapeutic potential for myocardial regeneration.
