Aberrant Wnt activation in recurrent genetically variant human pluripotent stem cells impairs cardiomyocyte differentiation and phenotype
Aberrant Wnt activation in recurrent genetically variant human pluripotent stem cells impairs cardiomyocyte differentiation and phenotype
复制标题
复发性遗传变异人多能干细胞中异常的 Wnt 激活损害心肌细胞分化和表型
DOI：
10.1101/2023.12.12.571269
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Wing T
中科院分区：
文献类型：
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作者：
Wing T
人类多能干细胞（hPSC）衍生的心肌细胞已成为疾病建模和细胞治疗的有力工具。从hPSC产生心肌细胞通常需要扩增大量的hPSC并将它们在培养物中维持延长的时间段。这反过来又使hPSC易于获得非随机遗传变化，包括染色体1q的复发性增益。在这里，我们表明，在hPSC中染色体1q的获得影响分化为心肌细胞的效率和分化细胞的表型。从机制上讲，我们发现Wnt信号通路的异常激活支持了变体1q hPSC的偏斜分化。总的来说，我们的数据表明，培养物中遗传变异细胞的存在是生产用于研究或临床应用的hPSC衍生的心肌细胞的重要问题。此外，我们的研究结果为将来的临床应用提供了去除遗传变异细胞的新方法。
Human pluripotent stem cell (hPSC)-derived cardiomyocytes have emerged as powerful tools for disease modelling and cell therapy. The production of cardiomyocytes from hPSCs typically requires expanding large numbers of hPSCs and maintaining them in culture for extended periods of time. This in turn predisposes hPSCs to the acquisition of non-random genetic changes, including recurrent gains of chromosome 1q. Here, we show that gain of chromosome 1q in hPSCs affects both the efficiency of differentiation to cardiomyocytes and phenotype of the differentiated cells. Mechanistically, we show that aberrant activation of the Wnt signalling pathway underpins the skewed differentiation of variant 1q hPSCs. Collectively, our data demonstrates that the presence of genetically variant cells in cultures is a significant concern for production of hPSC-derived cardiomyocytes for research or clinical applications. Further, our results suggest new approaches for removing genetically variant cells for future clinical applications.
DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
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作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W