Exosomal-ribosomal proteins-driven heterogeneity of epicardial adipose tissue derived stem cells under ischemia for cardiac regeneration
Corresponding Author
Finosh G. Thankam
Department of Translational Research, Western University of Health Sciences, Pomona, California, USA
Correspondence
Finosh G. Thankam, Department of Translational Research, Western University of Health Sciences, 309 E. Second Street, Pomona, California 91766-1854, USA.
Email: [email protected]
Contribution: Conceptualization, Methodology, Data curation, Formal analysis, Investigation, Writing - original draft, Writing - review & editing, Project administration, Supervision, Validation, Resources
Search for more papers by this authorJames Huynh
Department of Translational Research, Western University of Health Sciences, Pomona, California, USA
Contribution: Methodology, Data curation, Formal analysis, Investigation, Writing - review & editing
Search for more papers by this authorWilliam Fang
Department of Translational Research, Western University of Health Sciences, Pomona, California, USA
Contribution: Methodology, Data curation, Formal analysis, Investigation, Writing - review & editing
Search for more papers by this authorYu Chen
Molecular Instrumentation Center, University of California-Los Angeles, Los Angeles, California, USA
Contribution: Methodology, Data curation, Formal analysis, Writing - review & editing
Search for more papers by this authorDevendra K. Agrawal
Department of Translational Research, Western University of Health Sciences, Pomona, California, USA
Contribution: Methodology, Data curation, Formal analysis, Resources, Writing - review & editing
Search for more papers by this authorCorresponding Author
Finosh G. Thankam
Department of Translational Research, Western University of Health Sciences, Pomona, California, USA
Correspondence
Finosh G. Thankam, Department of Translational Research, Western University of Health Sciences, 309 E. Second Street, Pomona, California 91766-1854, USA.
Email: [email protected]
Contribution: Conceptualization, Methodology, Data curation, Formal analysis, Investigation, Writing - original draft, Writing - review & editing, Project administration, Supervision, Validation, Resources
Search for more papers by this authorJames Huynh
Department of Translational Research, Western University of Health Sciences, Pomona, California, USA
Contribution: Methodology, Data curation, Formal analysis, Investigation, Writing - review & editing
Search for more papers by this authorWilliam Fang
Department of Translational Research, Western University of Health Sciences, Pomona, California, USA
Contribution: Methodology, Data curation, Formal analysis, Investigation, Writing - review & editing
Search for more papers by this authorYu Chen
Molecular Instrumentation Center, University of California-Los Angeles, Los Angeles, California, USA
Contribution: Methodology, Data curation, Formal analysis, Writing - review & editing
Search for more papers by this authorDevendra K. Agrawal
Department of Translational Research, Western University of Health Sciences, Pomona, California, USA
Contribution: Methodology, Data curation, Formal analysis, Resources, Writing - review & editing
Search for more papers by this authorAbstract
Extracellular ribosomal proteins secreted in exosomes elicit biological/regenerative responses; however, ribosomal proteins contained in the exosomes of ischemia-challenged epicardial adipose tissue-derived stem cells (EATDS) remain unexplored. This study focuses on the identification of ribosomal proteins in the exosomes of ischemia-challenged EATDS and their sub-populations based on the key ribosomal proteins using single-cell genomics. Exosomes were isolated from control, ischemic (ISC), and reperfused (ISC/R) EATDS harvested from hyperlipidemic microswine, and the proteins were detected using Liquid chromatography with tandem mass spectrometry (LC-MS/MS). One hundred ninety-nine proteins and 177 proteins were detected in ISC and ISC/R groups, respectively with significant fold-change compared to controls. Five ribosomal proteins, RPL10A, 40SRPS18, 40SRPS30, 60SRPL14, and 40SRPSA, were significant owing to their abundance based on LC-MS/MS data. Expression of these proteins, except RPL10A, at transcript and protein levels were lower in ISC group compared to the control. scRNAseq analysis revealed EATDS heterogeneity based on the upregulation of 40SRPSA, 40SRPL18, and 40SRPS18. Pro-inflammatory sub-populations upregulated CCL5, anti-inflammatory sub-population upregulated IL-11, proliferative sub-population upregulated cell cycle and DNA replication mediators, and non-proliferative population downregulated the cell cycle and DNA replication mediators. Overall, the functional role of extracellular ribosomal proteins in driving unique phenotypes of EATDS population offers promise for designing effective translational approaches for myocardial regeneration.
CONFLICT OF INTEREST
All the authors have read the manuscript and declare no conflict of interest. No writing assistance was utilized in the production of this manuscript.
Open Research
DATA AVAILABILITY STATEMENT
The data that support the findings of this study are available from the corresponding author upon reasonable request.
Supporting Information
| Filename | Description |
|---|---|
| term3289-sup-0001-suppl-data.docx1.5 MB | Supplementary Material S1 |
| term3289-sup-0002-suppl-data.docx162.4 KB | Supplementary Material S2 |
| term3289-sup-0003-suppl-data.docx806.4 KB | Supplementary Material S3 |
| term3289-sup-0004-suppl-data.docx1.1 MB | Supplementary Material S4 |
| term3289-sup-0005-suppl-data.docx1.2 MB | Supplementary Material S5 |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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