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Differentiation-Associated MicroRNA Alterations in Mouse Heart-Derived Sca-1(+)CD31(-) and Sca-1(+)CD31(+) Cells
Qiong Wu1, Jinxi Zhan1, Yun Li1
1School of Life Sciences, Guangxi Normal University, Guilin 541004, China; Guangxi Universities Key Laboratory of Stem Cell and Biopharmaceutical Technology, Guangxi Normal University, Guilin 541004, China; Research Center for Biomedical Sciences, Guangxi Normal University, Guilin 541004, China.
Insights
Cardiac stem cells (CSCs) maintain heart health. Researchers isolated Sca-1(+)CD31(-) CSCs, finding they are multipotent, unlike Sca-1(+)CD31(+) cells, suggesting distinct roles in cardiac repair.
Area of Science:
- Cardiovascular Biology
- Stem Cell Research
- Molecular Cardiology
Background:
- Cardiac resident stem/progenitor cells (CSCs/CPCs) are vital for myocardial homeostasis.
- Identifying pure CSC/CPC populations is challenging due to cellular heterogeneity.
- Sca-1(+) cells are abundant but may include non-stem cell types, complicating transplantation.
Purpose of the Study:
- To isolate distinct CSC/CPC subtypes using flow-activated cell sorting based on surface markers.
- To evaluate the differentiation potential of isolated CSC/CPC subtypes.
- To elucidate the molecular mechanisms underlying stemness differences between CSC/CPC subtypes.
Main Methods:
- Isolation of cardiac stem/progenitor cells using flow-activated cell sorting with specific surface antigens (Lin(-)CD45(-)Sca-1(+)CD31(-) and Lin(-)CD45(-)Sca-1(+)CD31(+)).
- Assessment of multipotency and differentiation capacity into various cardiac lineages.
- Integrated analysis of microRNA (miRNA) and messenger RNA (mRNA) expression profiles.
Main Results:
- Mouse heart-derived Sca-1(+)CD31(-) cells demonstrated multipotency, differentiating into multiple cardiac lineages.
- Sca-1(+)CD31(+) cells lacked differentiation potential.
- A significant number of miRNAs and mRNAs were inversely associated with the stemness characteristics of the two subtypes, with mmu-miR-322-5p showing particular promise.
Conclusions:
- Cardiac stem/progenitor cell populations are heterogeneous, with distinct functional and differentiation capabilities.
- The Sca-1(+)CD31(-) subtype represents a multipotent cardiac stem cell population.
- Molecular profiling identified key miRNAs, such as mmu-miR-322-5p, potentially regulating CSC/CPC stemness and differentiation.
Abstract:
Cardiac resident stem/progenitor cells (CSC/CPCs) are critical to the cellular and functional integrity of the heart because they maintain myocardial cell homeostasis. Several populations of CSC/CPCs have been identified based on expression of different stem cell-associated antigens. Sca-1(+) cells in the cardiac tissue may be the most common CSC/CPCs. However, they are a heterogeneous cell population and, in transplants, clinicians might transplant more endothelial cells, cardiomyocytes, or other cells than stem cells. The purposes of this study were to (1) isolate CSC/CPCs with Lin(-)CD45(-)Sca-1(+)CD31(-) and Lin(-)CD45(-)Sca-1(+)CD31(+) surface antigens using flow-activated cell sorting; (2) investigate their differentiation potential; and (3) determine the molecular basis for differences in stemness characteristics between cell subtypes. The results indicated that mouse heart-derived Sca-1(+)CD31(-) cells were multipotent and retained the ability to differentiate into different cardiac cell lineages, but Sca-1(+)CD31(+) cells did not. Integrated analysis of microRNA and mRNA expression indicated that 20 microRNAs and 49 mRNAs were inversely associated with Sca-1(+)CD31(-) and Sca-1(+)CD31(+) subtype stemness characteristics. In particular, mmu-miR-322-5p had more targeted and inversely associated genes and transcription factors and might have higher potential for CSC/CPCs differentiation.
