Molecular Analysis of Fetal and Adult Primary Human Liver Sinusoidal Endothelial Cells: A Comparison to Other Endothelial Cells
In humans, Factor VIII (F8) deficiency leads to hemophilia A and F8 is largely synthesized and secreted by the liver sinusoidal endothelial cells (LSECs). However, the specificity and characteristics of these cells in comparison to other endothelial cells is not well known. In this study, we perform...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2020-10-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/21/20/7776 |
| _version_ | 1797550323050479616 |
|---|---|
| author | Muhammad Ahmer Jamil Heike Singer Rawya Al-Rifai Nicole Nüsgen Melanie Rath Sascha Strauss Ioanna Andreou Johannes Oldenburg Osman El-Maarri |
| author_facet | Muhammad Ahmer Jamil Heike Singer Rawya Al-Rifai Nicole Nüsgen Melanie Rath Sascha Strauss Ioanna Andreou Johannes Oldenburg Osman El-Maarri |
| author_sort | Muhammad Ahmer Jamil |
| collection | DOAJ |
| description | In humans, Factor VIII (F8) deficiency leads to hemophilia A and F8 is largely synthesized and secreted by the liver sinusoidal endothelial cells (LSECs). However, the specificity and characteristics of these cells in comparison to other endothelial cells is not well known. In this study, we performed genome wide expression and CpG methylation profiling of fetal and adult human primary LSECs together with other fetal primary endothelial cells from lung (micro-vascular and arterial), and heart (micro-vascular). Our results reveal expression and methylation markers distinguishing LSECs at both fetal and adult stages. Differential gene expression of fetal LSECs in comparison to other fetal endothelial cells pointed to several differentially regulated pathways and biofunctions in fetal LSECs. We used targeted bisulfite resequencing to confirm selected top differentially methylated regions. We further designed an assay where we used the selected methylation markers to test the degree of similarity of in-house iPS generated vascular endothelial cells to primary LSECs; a higher similarity was found to fetal than to adult LSECs. In this study, we provide a detailed molecular profile of LSECs and a guide to testing the effectiveness of production of in vitro differentiated LSECs. |
| first_indexed | 2024-03-10T15:27:39Z |
| format | Article |
| id | doaj.art-7d68a20517fc4dcfb9eba7db7b3fa969 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T15:27:39Z |
| publishDate | 2020-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-7d68a20517fc4dcfb9eba7db7b3fa9692023-11-20T17:54:00ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-10-012120777610.3390/ijms21207776Molecular Analysis of Fetal and Adult Primary Human Liver Sinusoidal Endothelial Cells: A Comparison to Other Endothelial CellsMuhammad Ahmer Jamil0Heike Singer1Rawya Al-Rifai2Nicole Nüsgen3Melanie Rath4Sascha Strauss5Ioanna Andreou6Johannes Oldenburg7Osman El-Maarri8Institute of Experimental Hematology and Transfusion Medicine, University of Bonn, Venusberg-Campus 1, 53127 Bonn, GermanyInstitute of Experimental Hematology and Transfusion Medicine, University of Bonn, Venusberg-Campus 1, 53127 Bonn, GermanyInstitute of Experimental Hematology and Transfusion Medicine, University of Bonn, Venusberg-Campus 1, 53127 Bonn, GermanyInstitute of Experimental Hematology and Transfusion Medicine, University of Bonn, Venusberg-Campus 1, 53127 Bonn, GermanyInstitute of Experimental Hematology and Transfusion Medicine, University of Bonn, Venusberg-Campus 1, 53127 Bonn, GermanyQiagen GmbH, 40724 Hilden, GermanyQiagen GmbH, 40724 Hilden, GermanyInstitute of Experimental Hematology and Transfusion Medicine, University of Bonn, Venusberg-Campus 1, 53127 Bonn, GermanyInstitute of Experimental Hematology and Transfusion Medicine, University of Bonn, Venusberg-Campus 1, 53127 Bonn, GermanyIn humans, Factor VIII (F8) deficiency leads to hemophilia A and F8 is largely synthesized and secreted by the liver sinusoidal endothelial cells (LSECs). However, the specificity and characteristics of these cells in comparison to other endothelial cells is not well known. In this study, we performed genome wide expression and CpG methylation profiling of fetal and adult human primary LSECs together with other fetal primary endothelial cells from lung (micro-vascular and arterial), and heart (micro-vascular). Our results reveal expression and methylation markers distinguishing LSECs at both fetal and adult stages. Differential gene expression of fetal LSECs in comparison to other fetal endothelial cells pointed to several differentially regulated pathways and biofunctions in fetal LSECs. We used targeted bisulfite resequencing to confirm selected top differentially methylated regions. We further designed an assay where we used the selected methylation markers to test the degree of similarity of in-house iPS generated vascular endothelial cells to primary LSECs; a higher similarity was found to fetal than to adult LSECs. In this study, we provide a detailed molecular profile of LSECs and a guide to testing the effectiveness of production of in vitro differentiated LSECs.https://www.mdpi.com/1422-0067/21/20/7776LSECsHHSECHCMECHPAECHPMECexpression profiling |
| spellingShingle | Muhammad Ahmer Jamil Heike Singer Rawya Al-Rifai Nicole Nüsgen Melanie Rath Sascha Strauss Ioanna Andreou Johannes Oldenburg Osman El-Maarri Molecular Analysis of Fetal and Adult Primary Human Liver Sinusoidal Endothelial Cells: A Comparison to Other Endothelial Cells International Journal of Molecular Sciences LSECs HHSEC HCMEC HPAEC HPMEC expression profiling |
| title | Molecular Analysis of Fetal and Adult Primary Human Liver Sinusoidal Endothelial Cells: A Comparison to Other Endothelial Cells |
| title_full | Molecular Analysis of Fetal and Adult Primary Human Liver Sinusoidal Endothelial Cells: A Comparison to Other Endothelial Cells |
| title_fullStr | Molecular Analysis of Fetal and Adult Primary Human Liver Sinusoidal Endothelial Cells: A Comparison to Other Endothelial Cells |
| title_full_unstemmed | Molecular Analysis of Fetal and Adult Primary Human Liver Sinusoidal Endothelial Cells: A Comparison to Other Endothelial Cells |
| title_short | Molecular Analysis of Fetal and Adult Primary Human Liver Sinusoidal Endothelial Cells: A Comparison to Other Endothelial Cells |
| title_sort | molecular analysis of fetal and adult primary human liver sinusoidal endothelial cells a comparison to other endothelial cells |
| topic | LSECs HHSEC HCMEC HPAEC HPMEC expression profiling |
| url | https://www.mdpi.com/1422-0067/21/20/7776 |
| work_keys_str_mv | AT muhammadahmerjamil molecularanalysisoffetalandadultprimaryhumanliversinusoidalendothelialcellsacomparisontootherendothelialcells AT heikesinger molecularanalysisoffetalandadultprimaryhumanliversinusoidalendothelialcellsacomparisontootherendothelialcells AT rawyaalrifai molecularanalysisoffetalandadultprimaryhumanliversinusoidalendothelialcellsacomparisontootherendothelialcells AT nicolenusgen molecularanalysisoffetalandadultprimaryhumanliversinusoidalendothelialcellsacomparisontootherendothelialcells AT melanierath molecularanalysisoffetalandadultprimaryhumanliversinusoidalendothelialcellsacomparisontootherendothelialcells AT saschastrauss molecularanalysisoffetalandadultprimaryhumanliversinusoidalendothelialcellsacomparisontootherendothelialcells AT ioannaandreou molecularanalysisoffetalandadultprimaryhumanliversinusoidalendothelialcellsacomparisontootherendothelialcells AT johannesoldenburg molecularanalysisoffetalandadultprimaryhumanliversinusoidalendothelialcellsacomparisontootherendothelialcells AT osmanelmaarri molecularanalysisoffetalandadultprimaryhumanliversinusoidalendothelialcellsacomparisontootherendothelialcells |