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Recessive cardiac phenotypes in induced pluripotent stem cell models of Jervell and Lange-Nielsen syndrome: Disease mechanisms and pharmacological rescue
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| Zeitschriftentitel: | Proceedings of the National Academy of Sciences |
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| Personen und Körperschaften: | , , , , , , , , , , , , , , |
| In: | Proceedings of the National Academy of Sciences, 111, 2014, 50 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
Proceedings of the National Academy of Sciences
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| Schlagwörter: |
| author_facet |
Zhang, Miao D’Aniello, Cristina Verkerk, Arie O. Wrobel, Eva Frank, Stefan Ward-van Oostwaard, Dorien Piccini, Ilaria Freund, Christian Rao, Jyoti Seebohm, Guiscard Atsma, Douwe E. Schulze-Bahr, Eric Mummery, Christine L. Greber, Boris Bellin, Milena Zhang, Miao D’Aniello, Cristina Verkerk, Arie O. Wrobel, Eva Frank, Stefan Ward-van Oostwaard, Dorien Piccini, Ilaria Freund, Christian Rao, Jyoti Seebohm, Guiscard Atsma, Douwe E. Schulze-Bahr, Eric Mummery, Christine L. Greber, Boris Bellin, Milena |
|---|---|
| author |
Zhang, Miao D’Aniello, Cristina Verkerk, Arie O. Wrobel, Eva Frank, Stefan Ward-van Oostwaard, Dorien Piccini, Ilaria Freund, Christian Rao, Jyoti Seebohm, Guiscard Atsma, Douwe E. Schulze-Bahr, Eric Mummery, Christine L. Greber, Boris Bellin, Milena |
| spellingShingle |
Zhang, Miao D’Aniello, Cristina Verkerk, Arie O. Wrobel, Eva Frank, Stefan Ward-van Oostwaard, Dorien Piccini, Ilaria Freund, Christian Rao, Jyoti Seebohm, Guiscard Atsma, Douwe E. Schulze-Bahr, Eric Mummery, Christine L. Greber, Boris Bellin, Milena Proceedings of the National Academy of Sciences Recessive cardiac phenotypes in induced pluripotent stem cell models of Jervell and Lange-Nielsen syndrome: Disease mechanisms and pharmacological rescue Multidisciplinary |
| author_sort |
zhang, miao |
| spelling |
Zhang, Miao D’Aniello, Cristina Verkerk, Arie O. Wrobel, Eva Frank, Stefan Ward-van Oostwaard, Dorien Piccini, Ilaria Freund, Christian Rao, Jyoti Seebohm, Guiscard Atsma, Douwe E. Schulze-Bahr, Eric Mummery, Christine L. Greber, Boris Bellin, Milena 0027-8424 1091-6490 Proceedings of the National Academy of Sciences Multidisciplinary http://dx.doi.org/10.1073/pnas.1419553111 <jats:title>Significance</jats:title> <jats:p> There are few laboratory models that recapitulate human cardiac disease. Here, we created human cell models for Jervell and Lange-Nielsen syndrome (JLNS) in vitro, based on human induced pluripotent stem cells (hiPSCs). JLNS is one of the most severe disorders of heart rhythm and can cause sudden death in young patients. JLNS is inherited recessively and is caused by homozygous mutations in the slow component of the delayed rectifier potassium current, I <jats:sub>Ks</jats:sub> . Cardiomyocytes (CMs) from two independent sets of patient-derived and engineered hiPSCs showed electrophysiological defects that reflect the severity of the condition in patients. Our work allowed better understanding of the mechanisms of recessive inheritance. Furthermore, JLNS-CMs showed increased sensitivity to proarrhythmic drugs, which could be rescued pharmacologically, demonstrating the potential of hiPSC-CMs in drug testing. </jats:p> Recessive cardiac phenotypes in induced pluripotent stem cell models of Jervell and Lange-Nielsen syndrome: Disease mechanisms and pharmacological rescue Proceedings of the National Academy of Sciences |
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| title |
Recessive cardiac phenotypes in induced pluripotent stem cell models of Jervell and Lange-Nielsen syndrome: Disease mechanisms and pharmacological rescue |
| title_unstemmed |
Recessive cardiac phenotypes in induced pluripotent stem cell models of Jervell and Lange-Nielsen syndrome: Disease mechanisms and pharmacological rescue |
| title_full |
Recessive cardiac phenotypes in induced pluripotent stem cell models of Jervell and Lange-Nielsen syndrome: Disease mechanisms and pharmacological rescue |
| title_fullStr |
Recessive cardiac phenotypes in induced pluripotent stem cell models of Jervell and Lange-Nielsen syndrome: Disease mechanisms and pharmacological rescue |
| title_full_unstemmed |
Recessive cardiac phenotypes in induced pluripotent stem cell models of Jervell and Lange-Nielsen syndrome: Disease mechanisms and pharmacological rescue |
| title_short |
Recessive cardiac phenotypes in induced pluripotent stem cell models of Jervell and Lange-Nielsen syndrome: Disease mechanisms and pharmacological rescue |
| title_sort |
recessive cardiac phenotypes in induced pluripotent stem cell models of jervell and lange-nielsen syndrome: disease mechanisms and pharmacological rescue |
| topic |
Multidisciplinary |
| url |
http://dx.doi.org/10.1073/pnas.1419553111 |
| publishDate |
2014 |
| physical |
|
| description |
<jats:title>Significance</jats:title>
<jats:p>
There are few laboratory models that recapitulate human cardiac disease. Here, we created human cell models for Jervell and Lange-Nielsen syndrome (JLNS) in vitro, based on human induced pluripotent stem cells (hiPSCs). JLNS is one of the most severe disorders of heart rhythm and can cause sudden death in young patients. JLNS is inherited recessively and is caused by homozygous mutations in the slow component of the delayed rectifier potassium current, I
<jats:sub>Ks</jats:sub>
. Cardiomyocytes (CMs) from two independent sets of patient-derived and engineered hiPSCs showed electrophysiological defects that reflect the severity of the condition in patients. Our work allowed better understanding of the mechanisms of recessive inheritance. Furthermore, JLNS-CMs showed increased sensitivity to proarrhythmic drugs, which could be rescued pharmacologically, demonstrating the potential of hiPSC-CMs in drug testing.
</jats:p> |
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| author | Zhang, Miao, D’Aniello, Cristina, Verkerk, Arie O., Wrobel, Eva, Frank, Stefan, Ward-van Oostwaard, Dorien, Piccini, Ilaria, Freund, Christian, Rao, Jyoti, Seebohm, Guiscard, Atsma, Douwe E., Schulze-Bahr, Eric, Mummery, Christine L., Greber, Boris, Bellin, Milena |
| author_facet | Zhang, Miao, D’Aniello, Cristina, Verkerk, Arie O., Wrobel, Eva, Frank, Stefan, Ward-van Oostwaard, Dorien, Piccini, Ilaria, Freund, Christian, Rao, Jyoti, Seebohm, Guiscard, Atsma, Douwe E., Schulze-Bahr, Eric, Mummery, Christine L., Greber, Boris, Bellin, Milena, Zhang, Miao, D’Aniello, Cristina, Verkerk, Arie O., Wrobel, Eva, Frank, Stefan, Ward-van Oostwaard, Dorien, Piccini, Ilaria, Freund, Christian, Rao, Jyoti, Seebohm, Guiscard, Atsma, Douwe E., Schulze-Bahr, Eric, Mummery, Christine L., Greber, Boris, Bellin, Milena |
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| description | <jats:title>Significance</jats:title> <jats:p> There are few laboratory models that recapitulate human cardiac disease. Here, we created human cell models for Jervell and Lange-Nielsen syndrome (JLNS) in vitro, based on human induced pluripotent stem cells (hiPSCs). JLNS is one of the most severe disorders of heart rhythm and can cause sudden death in young patients. JLNS is inherited recessively and is caused by homozygous mutations in the slow component of the delayed rectifier potassium current, I <jats:sub>Ks</jats:sub> . Cardiomyocytes (CMs) from two independent sets of patient-derived and engineered hiPSCs showed electrophysiological defects that reflect the severity of the condition in patients. Our work allowed better understanding of the mechanisms of recessive inheritance. Furthermore, JLNS-CMs showed increased sensitivity to proarrhythmic drugs, which could be rescued pharmacologically, demonstrating the potential of hiPSC-CMs in drug testing. </jats:p> |
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| spelling | Zhang, Miao D’Aniello, Cristina Verkerk, Arie O. Wrobel, Eva Frank, Stefan Ward-van Oostwaard, Dorien Piccini, Ilaria Freund, Christian Rao, Jyoti Seebohm, Guiscard Atsma, Douwe E. Schulze-Bahr, Eric Mummery, Christine L. Greber, Boris Bellin, Milena 0027-8424 1091-6490 Proceedings of the National Academy of Sciences Multidisciplinary http://dx.doi.org/10.1073/pnas.1419553111 <jats:title>Significance</jats:title> <jats:p> There are few laboratory models that recapitulate human cardiac disease. Here, we created human cell models for Jervell and Lange-Nielsen syndrome (JLNS) in vitro, based on human induced pluripotent stem cells (hiPSCs). JLNS is one of the most severe disorders of heart rhythm and can cause sudden death in young patients. JLNS is inherited recessively and is caused by homozygous mutations in the slow component of the delayed rectifier potassium current, I <jats:sub>Ks</jats:sub> . Cardiomyocytes (CMs) from two independent sets of patient-derived and engineered hiPSCs showed electrophysiological defects that reflect the severity of the condition in patients. Our work allowed better understanding of the mechanisms of recessive inheritance. Furthermore, JLNS-CMs showed increased sensitivity to proarrhythmic drugs, which could be rescued pharmacologically, demonstrating the potential of hiPSC-CMs in drug testing. </jats:p> Recessive cardiac phenotypes in induced pluripotent stem cell models of Jervell and Lange-Nielsen syndrome: Disease mechanisms and pharmacological rescue Proceedings of the National Academy of Sciences |
| spellingShingle | Zhang, Miao, D’Aniello, Cristina, Verkerk, Arie O., Wrobel, Eva, Frank, Stefan, Ward-van Oostwaard, Dorien, Piccini, Ilaria, Freund, Christian, Rao, Jyoti, Seebohm, Guiscard, Atsma, Douwe E., Schulze-Bahr, Eric, Mummery, Christine L., Greber, Boris, Bellin, Milena, Proceedings of the National Academy of Sciences, Recessive cardiac phenotypes in induced pluripotent stem cell models of Jervell and Lange-Nielsen syndrome: Disease mechanisms and pharmacological rescue, Multidisciplinary |
| title | Recessive cardiac phenotypes in induced pluripotent stem cell models of Jervell and Lange-Nielsen syndrome: Disease mechanisms and pharmacological rescue |
| title_full | Recessive cardiac phenotypes in induced pluripotent stem cell models of Jervell and Lange-Nielsen syndrome: Disease mechanisms and pharmacological rescue |
| title_fullStr | Recessive cardiac phenotypes in induced pluripotent stem cell models of Jervell and Lange-Nielsen syndrome: Disease mechanisms and pharmacological rescue |
| title_full_unstemmed | Recessive cardiac phenotypes in induced pluripotent stem cell models of Jervell and Lange-Nielsen syndrome: Disease mechanisms and pharmacological rescue |
| title_short | Recessive cardiac phenotypes in induced pluripotent stem cell models of Jervell and Lange-Nielsen syndrome: Disease mechanisms and pharmacological rescue |
| title_sort | recessive cardiac phenotypes in induced pluripotent stem cell models of jervell and lange-nielsen syndrome: disease mechanisms and pharmacological rescue |
| title_unstemmed | Recessive cardiac phenotypes in induced pluripotent stem cell models of Jervell and Lange-Nielsen syndrome: Disease mechanisms and pharmacological rescue |
| topic | Multidisciplinary |
| url | http://dx.doi.org/10.1073/pnas.1419553111 |