1. Cardiopulmonary progenitors facilitate cardiac repair via exosomal transfer of miR-27b-3p targeting the SIK1-CREB1 axis.
- Author
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Xiao YY, Xia LX, Jiang WJ, Qin JF, Zhao LX, Li Z, Huang LJ, Li KX, Yu PJ, Wei L, Jiang XY, Chen ZS, and Yu XY
- Subjects
- Animals, Mice, Protein Serine-Threonine Kinases metabolism, Protein Serine-Threonine Kinases genetics, Myocardial Infarction metabolism, Myocardial Infarction genetics, Myocardial Infarction therapy, Stem Cells metabolism, Stem Cells cytology, Cell Proliferation, Cell Differentiation, Lung metabolism, Mice, Inbred C57BL, Myocardium metabolism, Myocardium cytology, MicroRNAs genetics, MicroRNAs metabolism, Exosomes metabolism, Cyclic AMP Response Element-Binding Protein metabolism, Cyclic AMP Response Element-Binding Protein genetics
- Abstract
Ischemic heart disease, especially myocardial infarction (MI), is one of the leading causes of death worldwide, and desperately needs effective treatments, such as cell therapy. Cardiopulmonary progenitors (CPPs) are stem cells for both heart and lung, but their repairing role in damaged heart is still unknown. Here, we obtained CPPs from E9.5 mouse embryos, maintained their stemness while expanding, and identified their characteristics by scRNA-seq, flow cytometry, quantitative reverse transcription-polymerase chain reaction, and differentiation assays. Moreover, we employed mouse MI model to investigate whether CPPs could repair the injured heart. Our data identified that CPPs exhibit hybrid fibroblastic, endothelial, and mesenchymal state, and they could differentiate into cell lineages within the cardiopulmonary system. Moreover, intramyocardial injection of CPPs improves cardiac function through CPPs exosomes (CPPs-Exo) by promotion of cardiomyocytic proliferation and vascularization. To uncover the underlying mechanism, we used miRNA-seq, bulk RNA-seq, and bioinformatic approaches, and found the highly expressed miR-27b-3p in CPPs-Exo and its target gene Sik1, which can influence the transcriptional activity of CREB1. Therefore, we postulate that CPPs facilitate cardiac repair partially through the SIK1-CREB1 axis via exosomal miR-27b-3p. Our study offers a novel insight into the role of CPPs-Exo in heart repair and highlights the potential of CPPs-Exo as a promising therapeutic strategy for MI., (© 2024 The Authors. Cell Proliferation published by Beijing Institute for Stem Cell and Regenerative Medicine and John Wiley & Sons Ltd.)
- Published
- 2024
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