Lovastatin Decreases the Expression of CD133 and Influences the Differentiation Potential of Human Embryonic Stem Cells
The lipophilic statin lovastatin decreases cholesterol synthesis and is a safe and effective treatment for the prevention of cardiovascular diseases. Growing evidence points at antitumor potential of lovastatin. Therefore, understanding the molecular mechanism of lovastatin function in different cel...
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| Format: | Article |
| Language: | English |
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Wiley
2016-01-01
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| Series: | Stem Cells International |
| Online Access: | http://dx.doi.org/10.1155/2016/1580701 |
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| _version_ | 1832566194686656512 |
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| author | Ade Kallas-Kivi Annika Trei Toivo Maimets |
| author_facet | Ade Kallas-Kivi Annika Trei Toivo Maimets |
| author_sort | Ade Kallas-Kivi |
| collection | DOAJ |
| description | The lipophilic statin lovastatin decreases cholesterol synthesis and is a safe and effective treatment for the prevention of cardiovascular diseases. Growing evidence points at antitumor potential of lovastatin. Therefore, understanding the molecular mechanism of lovastatin function in different cell types is critical to effective therapy design. In this study, we investigated the effects of lovastatin on the differentiation potential of human embryonic stem (hES) cells (H9 cell line). Multiparameter flow cytometric assay was used to detect changes in the expression of transcription factors characteristic of hES cells. We found that lovastatin treatment delayed NANOG downregulation during ectodermal and endodermal differentiation. Likewise, expression of ectodermal (SOX1 and OTX2) and endodermal (GATA4 and FOXA2) markers was higher in treated cells. Exposure of hES cells to lovastatin led to a minor decrease in the expression of SSEA-3 and a significant reduction in CD133 expression. Treated cells also formed fewer embryoid bodies than control cells. By analyzing hES with and without CD133, we discovered that CD133 expression is required for proper formation of embryoid bodies. In conclusion, lovastatin reduced the heterogeneity of hES cells and impaired their differentiation potential. |
| format | Article |
| id | doaj-art-37cc1f4f69de465fa8df3fb699395129 |
| institution | Kabale University |
| issn | 1687-966X 1687-9678 |
| language | English |
| publishDate | 2016-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Stem Cells International |
| spelling | doaj-art-37cc1f4f69de465fa8df3fb6993951292025-02-03T01:04:48ZengWileyStem Cells International1687-966X1687-96782016-01-01201610.1155/2016/15807011580701Lovastatin Decreases the Expression of CD133 and Influences the Differentiation Potential of Human Embryonic Stem CellsAde Kallas-Kivi0Annika Trei1Toivo Maimets2Institute of Molecular and Cell Biology, University of Tartu, Riia 23, 51010 Tartu, EstoniaInstitute of Molecular and Cell Biology, University of Tartu, Riia 23, 51010 Tartu, EstoniaInstitute of Molecular and Cell Biology, University of Tartu, Riia 23, 51010 Tartu, EstoniaThe lipophilic statin lovastatin decreases cholesterol synthesis and is a safe and effective treatment for the prevention of cardiovascular diseases. Growing evidence points at antitumor potential of lovastatin. Therefore, understanding the molecular mechanism of lovastatin function in different cell types is critical to effective therapy design. In this study, we investigated the effects of lovastatin on the differentiation potential of human embryonic stem (hES) cells (H9 cell line). Multiparameter flow cytometric assay was used to detect changes in the expression of transcription factors characteristic of hES cells. We found that lovastatin treatment delayed NANOG downregulation during ectodermal and endodermal differentiation. Likewise, expression of ectodermal (SOX1 and OTX2) and endodermal (GATA4 and FOXA2) markers was higher in treated cells. Exposure of hES cells to lovastatin led to a minor decrease in the expression of SSEA-3 and a significant reduction in CD133 expression. Treated cells also formed fewer embryoid bodies than control cells. By analyzing hES with and without CD133, we discovered that CD133 expression is required for proper formation of embryoid bodies. In conclusion, lovastatin reduced the heterogeneity of hES cells and impaired their differentiation potential.http://dx.doi.org/10.1155/2016/1580701 |
| spellingShingle | Ade Kallas-Kivi Annika Trei Toivo Maimets Lovastatin Decreases the Expression of CD133 and Influences the Differentiation Potential of Human Embryonic Stem Cells Stem Cells International |
| title | Lovastatin Decreases the Expression of CD133 and Influences the Differentiation Potential of Human Embryonic Stem Cells |
| title_full | Lovastatin Decreases the Expression of CD133 and Influences the Differentiation Potential of Human Embryonic Stem Cells |
| title_fullStr | Lovastatin Decreases the Expression of CD133 and Influences the Differentiation Potential of Human Embryonic Stem Cells |
| title_full_unstemmed | Lovastatin Decreases the Expression of CD133 and Influences the Differentiation Potential of Human Embryonic Stem Cells |
| title_short | Lovastatin Decreases the Expression of CD133 and Influences the Differentiation Potential of Human Embryonic Stem Cells |
| title_sort | lovastatin decreases the expression of cd133 and influences the differentiation potential of human embryonic stem cells |
| url | http://dx.doi.org/10.1155/2016/1580701 |
| work_keys_str_mv | AT adekallaskivi lovastatindecreasestheexpressionofcd133andinfluencesthedifferentiationpotentialofhumanembryonicstemcells AT annikatrei lovastatindecreasestheexpressionofcd133andinfluencesthedifferentiationpotentialofhumanembryonicstemcells AT toivomaimets lovastatindecreasestheexpressionofcd133andinfluencesthedifferentiationpotentialofhumanembryonicstemcells |