biostudies-literatureXiao YYGuangzhou Medical UniversityGuangdong Provincial Drug Administration Science and Technology Innovation Project - Key Technology Research on Chest Disease Prevention and Treatment Drug Research and Clinical EvaluationChina Postdoctoral Science FoundationNational Natural Science Foundation of ChinaNatural Science Foundation of Guangdong ProvinceNational Key Research and Development Program of Chinae13593https://www.ebi.ac.uk/biostudies/studies/S-EPMC11056695biostudies-literatureUnknown57(5)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 lineagesCell proliferationCardiopulmonary progenitors facilitate cardiac repair via exosomal transfer of miR-27b-3p targeting the SIK1-CREB1 axis.PMC110566952022M7108902019A15150113002022ZDZ1006-410-210721106‐410‐2107211819002842022YFE0209700Huang LJXia LXZhao LXYu PJJiang XYLi KXJiang WJChen ZSLi ZQin JFXiao YYWei LYu XYfalseCardiopulmonary progenitors facilitate cardiac repair via exosomal transfer of miR-27b-3p targeting the SIK1-CREB1 axis.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 lineages2024-01-01T00:00:00Z2024 May2026-05-29T09:44:24.264Z2025-07-27T03:11:07.032ZS-EPMC110566953818575710.1111/cpr.13593