Gain of chromosome region 1q31.3 in human iPSCs confers growth advantage and alters contraction in derivative cardiomyocytes
SUMMARY hPSCs can acquire chromosomal aberrations such as copy number variations during prolonged maintenancein vitro, conferring growth advantages. However, the effect of these culture-acquired mutations on the phenotypes of the differentiated hPSCs is largely unstudied. Here, we identified mosaicism in a hPSC line in which some cells showed a gain of chromosome 1q31.3. We subcloned the wild-type and variant hPSCs and could maintain both as stable lines. While both variant and wildtype lines differentiated efficiently to cardiomyocytes (hPSC-CMs), molecular analysis revealed the variant hPSC-CMs had increased expression ofTNNT2, a gene encoding one of the major sarcomere proteins mediating cardiomyocyte contractility and located within the gained chromosome 1q region. Moreover, the variant hPSC-CMs showed altered contraction kinetics. Together these results highlight the importance of careful monitoring of chromosome aberrations in hPSC lines as these could have confounding effects in various applications such as disease modelling and drug discovery..
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Preprint| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
bioRxiv.org - (2023) vom: 14. Dez. Zur Gesamtaufnahme - year:2023 |
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| Sprache: |
Englisch |
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| Beteiligte Personen: |
Brandão, Karina O. [VerfasserIn] |
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| Links: |
Volltext [kostenfrei] |
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| doi: |
10.1101/2023.12.11.571144 |
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| PPN (Katalog-ID): |
XBI041849833 |
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| 245 | 1 | 0 | |a Gain of chromosome region 1q31.3 in human iPSCs confers growth advantage and alters contraction in derivative cardiomyocytes |
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| 520 | |a SUMMARY hPSCs can acquire chromosomal aberrations such as copy number variations during prolonged maintenancein vitro, conferring growth advantages. However, the effect of these culture-acquired mutations on the phenotypes of the differentiated hPSCs is largely unstudied. Here, we identified mosaicism in a hPSC line in which some cells showed a gain of chromosome 1q31.3. We subcloned the wild-type and variant hPSCs and could maintain both as stable lines. While both variant and wildtype lines differentiated efficiently to cardiomyocytes (hPSC-CMs), molecular analysis revealed the variant hPSC-CMs had increased expression ofTNNT2, a gene encoding one of the major sarcomere proteins mediating cardiomyocyte contractility and located within the gained chromosome 1q region. Moreover, the variant hPSC-CMs showed altered contraction kinetics. Together these results highlight the importance of careful monitoring of chromosome aberrations in hPSC lines as these could have confounding effects in various applications such as disease modelling and drug discovery. | ||
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| 700 | 1 | |a Salvatori, Daniela |4 aut | |
| 700 | 1 | |a Cao, Xu |4 aut | |
| 700 | 1 | |a Sala, Luca |0 (orcid)0000-0002-4129-6632 |4 aut | |
| 700 | 1 | |a Yiangou, Loukia |4 aut | |
| 700 | 1 | |a Mol, Mervyn P.H. |4 aut | |
| 700 | 1 | |a Bellin, Milena |4 aut | |
| 700 | 1 | |a Mummery, Christine L. |4 aut | |
| 700 | 1 | |a Davis, Richard P. |0 (orcid)0000-0002-7917-9423 |4 aut | |
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