scholarly journals Single-cell transcriptomic profiling and characterization of endothelial progenitor cells: new approach for finding novel markers

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Mohamed Essameldin Abdelgawad ◽  
Christophe Desterke ◽  
Georges Uzan ◽  
Sina Naserian

Abstract Background Endothelial progenitor cells (EPCs) are promising candidates for the cellular therapy of peripheral arterial and cardiovascular diseases. However, hitherto there is no specific marker(s) defining precisely EPCs. Herein, we are proposing a new in silico approach for finding novel EPC markers. Methods We assembled five groups of chosen EPC-related genes/factors using PubMed literature and Gene Ontology databases. This shortened database of EPC factors was fed into publically published transcriptome matrix to compare their expression between endothelial colony-forming cells (ECFCs), HUVECs, and two adult endothelial cell types (ECs) from the skin and adipose tissue. Further, the database was used for functional enrichment on Mouse Phenotype database and protein-protein interaction network analyses. Moreover, we built a digital matrix of healthy donors’ PBMCs (33 thousand single-cell transcriptomes) and analyzed the expression of these EPC factors. Results Transcriptome analyses showed that BMP2, 4, and ephrinB2 were exclusively highly expressed in EPCs; the expression of neuropilin-1 and VEGF-C were significantly higher in EPCs and HUVECs compared with other ECs; Notch 1 was highly expressed in EPCs and skin-ECs; MIR21 was highly expressed in skin-ECs; PECAM-1 was significantly higher in EPCs and adipose ECs. Moreover, functional enrichment of EPC-related genes on Mouse Phenotype and STRING protein database has revealed significant relations between chosen EPC factors and endothelial and vascular functions, development, and morphogenesis, where ephrinB2, BMP2, and BMP4 were highly expressed in EPCs and were connected to abnormal vascular functions. Single-cell RNA-sequencing analyses have revealed that among the EPC-regulated markers in transcriptome analyses, (i) ICAM1 and Endoglin were weekly expressed in the monocyte compartment of the peripheral blood; (ii) CD163 and CD36 were highly expressed in the CD14+ monocyte compartment whereas CSF1R was highly expressed in the CD16+ monocyte compartment, (iii) L-selectin and IL6R were globally expressed in the lymphoid/myeloid compartments, and (iv) interestingly, PLAUR/UPAR and NOTCH2 were highly expressed in both CD14+ and CD16+ monocytic compartments. Conclusions The current study has identified novel EPC markers that could be used for better characterization of EPC subpopulation in adult peripheral blood and subsequent usage of EPCs for various cell therapy and regenerative medicine applications.

2021 ◽  
Author(s):  
Mohamed Essameldin Abdelgawad ◽  
Christophe Desterke ◽  
Georges Uzan ◽  
Sina Naserian

Abstract Background: Endothelial progenitor cells (EPCs) are promising candidates for the cellular therapy of peripheral arterial & cardiovascular diseases. However, hitherto there is no specific marker(s) defining precisely EPCs. Herein, we are proposing a new in-silico approach for finding novel EPCs markers. Methods: we assembled five groups of chosen EPCs-related genes/factors using Pubmed literature & gene ontology databases. This shortened database of EPCs factors was fed into publically-published transcriptome matrix to compare their expression between endothelial colony-forming cells (ECFCs), HUVECs and two adult endothelial cell types (ECs) from skin and adipose tissue. Further, the database was used for functional enrichment on mouse phenotype database and protein-protein interaction network analyses. Moreover, we built a digital matrix of healthy donors' PBMCs (33 thousand single cell transcriptomes) and analyzed the expression of these EPCs factors Results: Transcriptome analyses showed that BMP2,4 & ephrinB2 were exclusively highly expressed in EPCs; the expression of neuropilin-1 & VEGF-C were significantly higher in EPCs & HUVECs compared with other ECs; Notch 1 was highly expressed in EPCs & skin-ECs; MIR21 was highly expressed in skin-ECs; PECAM-1 were significantly higher in EPCs & adipose ECs. Moreover, functional enrichment of EPCs-related genes on mouse phenotype and STRING protein database has revealed significant relations between chosen EPCs factors and endothelial & vascular functions, development and morphogenesis, where ephrinB2, BMP2 and BMP4 were highly expressed in EPCs and were connected to abnormal vascular functions. Single cell RNA-sequencing analyses has revealed that among the EPCs regulated markers in transcriptome analyses: i-ICAM1 & Endoglin were weekly expressed in the monocyte compartment of peripheral blood; ii-CD163 & CD36 were highly expressed in CD14+ monocyte compartment whereas CSF1R was highly expressed in CD16+ monocyte compartment; iii-L-selectin & IL6R were globally expressed in the lymphoid/myeloid compartments; iv-interestingly, PLAUR/UPAR & NOTCH2 were highly expressed in both CD14+ & CD16+ monocytic compartments. Conclusions: The current study has identified novel EPCs markers that could be used for better characterization of EPCs sub-population in adult peripheral blood and subsequent usage of EPCs for various cell therapy and regenerative medicine applications.


2020 ◽  
Author(s):  
Mohamed Essameldin Abdelgawad ◽  
Christophe Desterke ◽  
Georges Uzan ◽  
Sina Naserian

Abstract Background: Endothelial progenitor cells (EPCs) are promising candidates for the cellular therapy of peripheral arterial & cardiovascular diseases. However, hitherto there is no specific marker(s) defining precisely EPCs. Herein, we are proposing a new in-silico approach for finding novel EPCs markers. Methods: we assembled five groups of chosen EPCs-related genes/factors using Pubmed literature & gene ontology databases. This shortened database of EPCs factors was fed into publically-published transcriptome matrix to compare their expression between endothelial colony-forming cells (ECFCs), HUVECs and two adult endothelial cell types (ECs) from skin and adipose tissue. Further, the database was used for functional enrichment on mouse phenotype database and protein-protein interaction network analyses. Moreover, we built a digital matrix of healthy donors' PBMCs (33 thousand single cell transcriptomes) and analyzed the expression of these EPCs factorsResults: Transcriptome analyses showed that BMP2,4 & ephrinB2 were exclusively highly expressed in EPCs; the expression of neuropilin-1 & VEGF-C were significantly higher in EPCs & HUVECs compared with other ECs; Notch 1 was highly expressed in EPCs & skin-ECs; MIR21 was highly expressed in skin-ECs; PECAM-1 were significantly higher in EPCs & adipose ECs. Moreover, functional enrichment of EPCs-related genes on mouse phenotype and STRING protein database has revealed significant relations between chosen EPCs factors and endothelial & vascular functions, development and morphogenesis, where ephrinB2, BMP2 and BMP4 were highly expressed in EPCs and were connected to abnormal vascular functions. Single cell RNA-sequencing analyses has revealed that among the EPCs regulated markers in transcriptome analyses: i-ICAM1 & Endoglin were weekly expressed in the monocyte compartment of peripheral blood; ii-CD163 & CD36 were highly expressed in CD14+ monocyte compartment whereas CSF1R was highly expressed in CD16+ monocyte compartment; iii-L-selectin & IL6R were globally expressed in the lymphoid/myeloid compartments; iv-interestingly, PLAUR/UPAR & NOTCH2 were highly expressed in both CD14+ & CD16+ monocytic compartments. Conclusions: The current study has identified novel EPCs markers that could be used for better characterization of EPCs sub-population in adult peripheral blood and subsequent usage of EPCs for various cell therapy and regenerative medicine applications.


2010 ◽  
Vol 93 (1) ◽  
pp. 123-125 ◽  
Author(s):  
Takashi Kimura ◽  
Hirao Kohno ◽  
Yoshikazu Matsuoka ◽  
Ryusuke Nakatsuka ◽  
Yutaka Sasaki ◽  
...  

Author(s):  
T. Bulduk ◽  
A. U. Yalcin ◽  
O. M. Akay ◽  
S. G. Ozkurt ◽  
H. U. Teke ◽  
...  

Anemia is a common complication of chronic kidney disease (CKD). The most common cause of anemia in CKD is erythropoietin deficiency; and the most important cause of mortality in CKD patients is atherosclerotic vascular complications which are associated with endothelial damage. One of the methods evaluating vascular integrity is the cytometric measurement of circulating endothelial cells and endothelial progenitor cells in peripheral blood. The study aimed to investigate the effects of erythropoietin therapy on endothelial dysfunction by evaluating circulating endothelial cells and endothelial progenitor cells in peripheral blood using the technique of flow cytometry. Methods. A total of 55 hemodialysis patients were evaluated in three groups; those having erythropoietin therapy for at least last 3 months (n = 20) / not having erythropoietin for at least the last 3 months (n = 20) and the patients who started erythropoietin treatment during the study (n = 5). The control group consisted of 20 people. Blood values of the 3rd Group were investigated three times as baseline, 2nd week and 8th week CD34 +, CD105 + cells were evaluated as activated circulating endothelial cells; CD133 +, CD146 + cells were evaluated as activated endothelial progenitor cells. Results. There was no difference between the patients and healthy individuals in terms of circulating endothelial cells and endothelial progenitor cells. In the third group, no differences were observed in circulating endothelial cells / endothelial progenitor cell levels at baseline / 2nd and 8th weeks. There was no correlation between erythropoietin and circulating endothelial cells / endothelial progenitor cells. Conclusion. A correlation is not available between the therapeutic doses of erythropoietin used in hemodialysis patients and circulating endothelial cells / endothelial progenitor cell levels; supratherapeutic doses could change the results.


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