Exogenous expression of human apoA-I enhances cardiac differentiation of pluripotent stem cells.
The cardioprotective effects of high-density lipoprotein cholesterol (HDL-C) and apolipoprotein A1 (apoA-I) are well documented, but their effects in the direction of the cardiac differentiation of embryonic stem cells are unknown. We evaluated the effects of exogenous apoA-I expression on cardiac d...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2011-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3092777?pdf=render |
| _version_ | 1818313739224481792 |
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| author | Kwong-Man Ng Yee-Ki Lee Wing-Hon Lai Yau-Chi Chan Man-Lung Fung Hung-Fat Tse Chung-Wah Siu |
| author_facet | Kwong-Man Ng Yee-Ki Lee Wing-Hon Lai Yau-Chi Chan Man-Lung Fung Hung-Fat Tse Chung-Wah Siu |
| author_sort | Kwong-Man Ng |
| collection | DOAJ |
| description | The cardioprotective effects of high-density lipoprotein cholesterol (HDL-C) and apolipoprotein A1 (apoA-I) are well documented, but their effects in the direction of the cardiac differentiation of embryonic stem cells are unknown. We evaluated the effects of exogenous apoA-I expression on cardiac differentiation of ESCs and maturation of ESC-derived cardiomyocytes. We stably over-expressed full-length human apoA-I cDNA with lentivirus (LV)-mediated gene transfer in undifferentiated mouse ESCs and human induced pluripotent stem cells. Upon cardiac differentiation, we observed a significantly higher percentage of beating embryoid bodies, an increased number of cardiomyocytes as determined by flow cytometry, and expression of cardiac markers including α-myosin heavy chain, β-myosin heavy chain and myosin light chain 2 ventricular transcripts in LV-apoA-I transduced ESCs compared with control (LV-GFP). In the presence of noggin, a BMP4 antagonist, activation of BMP4-SMAD signaling cascade in apoA-I transduced ESCs completely abolished the apoA-I stimulated cardiac differentiation. Furthermore, co-application of recombinant apoA-I and BMP4 synergistically increased the percentage of beating EBs derived from untransduced D3 ESCs. These together suggests that that pro-cardiogenic apoA-I is mediated via the BMP4-SMAD signaling pathway. Functionally, cardiomyocytes derived from the apoA-I-transduced cells exhibited improved calcium handling properties in both non-caffeine and caffeine-induced calcium transient, suggesting that apoA-I plays a role in enhancing cardiac maturation. This increased cardiac differentiation and maturation has also been observed in human iPSCs, providing further evidence of the beneficial effects of apoA-I in promoting cardiac differentiation. In Conclusion, we present novel experimental evidence that apoA-I enhances cardiac differentiation of ESCs and iPSCs and promotes maturation of the calcium handling property of ESC-derived cardiomyocytes via the BMP4/SMAD signaling pathway. |
| first_indexed | 2024-12-13T08:38:32Z |
| format | Article |
| id | doaj.art-5b66307713dd4b369004aebb8045f25a |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-13T08:38:32Z |
| publishDate | 2011-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-5b66307713dd4b369004aebb8045f25a2022-12-21T23:53:36ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-01-0165e1978710.1371/journal.pone.0019787Exogenous expression of human apoA-I enhances cardiac differentiation of pluripotent stem cells.Kwong-Man NgYee-Ki LeeWing-Hon LaiYau-Chi ChanMan-Lung FungHung-Fat TseChung-Wah SiuThe cardioprotective effects of high-density lipoprotein cholesterol (HDL-C) and apolipoprotein A1 (apoA-I) are well documented, but their effects in the direction of the cardiac differentiation of embryonic stem cells are unknown. We evaluated the effects of exogenous apoA-I expression on cardiac differentiation of ESCs and maturation of ESC-derived cardiomyocytes. We stably over-expressed full-length human apoA-I cDNA with lentivirus (LV)-mediated gene transfer in undifferentiated mouse ESCs and human induced pluripotent stem cells. Upon cardiac differentiation, we observed a significantly higher percentage of beating embryoid bodies, an increased number of cardiomyocytes as determined by flow cytometry, and expression of cardiac markers including α-myosin heavy chain, β-myosin heavy chain and myosin light chain 2 ventricular transcripts in LV-apoA-I transduced ESCs compared with control (LV-GFP). In the presence of noggin, a BMP4 antagonist, activation of BMP4-SMAD signaling cascade in apoA-I transduced ESCs completely abolished the apoA-I stimulated cardiac differentiation. Furthermore, co-application of recombinant apoA-I and BMP4 synergistically increased the percentage of beating EBs derived from untransduced D3 ESCs. These together suggests that that pro-cardiogenic apoA-I is mediated via the BMP4-SMAD signaling pathway. Functionally, cardiomyocytes derived from the apoA-I-transduced cells exhibited improved calcium handling properties in both non-caffeine and caffeine-induced calcium transient, suggesting that apoA-I plays a role in enhancing cardiac maturation. This increased cardiac differentiation and maturation has also been observed in human iPSCs, providing further evidence of the beneficial effects of apoA-I in promoting cardiac differentiation. In Conclusion, we present novel experimental evidence that apoA-I enhances cardiac differentiation of ESCs and iPSCs and promotes maturation of the calcium handling property of ESC-derived cardiomyocytes via the BMP4/SMAD signaling pathway.http://europepmc.org/articles/PMC3092777?pdf=render |
| spellingShingle | Kwong-Man Ng Yee-Ki Lee Wing-Hon Lai Yau-Chi Chan Man-Lung Fung Hung-Fat Tse Chung-Wah Siu Exogenous expression of human apoA-I enhances cardiac differentiation of pluripotent stem cells. PLoS ONE |
| title | Exogenous expression of human apoA-I enhances cardiac differentiation of pluripotent stem cells. |
| title_full | Exogenous expression of human apoA-I enhances cardiac differentiation of pluripotent stem cells. |
| title_fullStr | Exogenous expression of human apoA-I enhances cardiac differentiation of pluripotent stem cells. |
| title_full_unstemmed | Exogenous expression of human apoA-I enhances cardiac differentiation of pluripotent stem cells. |
| title_short | Exogenous expression of human apoA-I enhances cardiac differentiation of pluripotent stem cells. |
| title_sort | exogenous expression of human apoa i enhances cardiac differentiation of pluripotent stem cells |
| url | http://europepmc.org/articles/PMC3092777?pdf=render |
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