{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T15:32:52Z","timestamp":1772119972439,"version":"3.50.1"},"reference-count":27,"publisher":"Springer Science and Business Media LLC","issue":"4","license":[{"start":{"date-parts":[[2022,1,8]],"date-time":"2022-01-08T00:00:00Z","timestamp":1641600000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,1,8]],"date-time":"2022-01-08T00:00:00Z","timestamp":1641600000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Stem Cell Rev and Rep"],"published-print":{"date-parts":[[2022,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Human pluripotent stem cells (hPSCs) have great potential for disease modeling, drug discovery, and regenerative medicine as they can differentiate into many different functional cell types via directed differentiation. However, the application of disease modeling is limited due to a time-consuming and labor-intensive process of introducing known pathogenic mutations into hPSCs. Base editing is a newly developed technology that enables the facile introduction of point mutations into specific loci within the genome of living cells without unwanted genome injured. We describe an optimized stepwise protocol to introduce disease-specific mutations of long QT syndrome (LQTs) into hPSCs. We highlight technical issues, especially those associated with introducing a point mutation to obtain isogenic hPSCs without inserting any resistance cassette and reproducible cardiomyocyte differentiation. Based on the protocol, we succeeded in getting hPSCs carrying LQTs pathogenic mutation with excellent efficiency (31.7% of heterozygous clones, 9.1% of homozygous clones) in less than 20\u00a0days. In addition, we also provide protocols to analyze electrophysiological of hPSC-derived cardiomyocytes using multi-electrode arrays. This protocol is also applicable to introduce other disease-specific mutations into hPSCs.<\/jats:p>\n                  <jats:p>\n                    <jats:bold>Graphical abstract<\/jats:bold>\n                  <\/jats:p>","DOI":"10.1007\/s12015-021-10324-6","type":"journal-article","created":{"date-parts":[[2022,1,8]],"date-time":"2022-01-08T10:02:27Z","timestamp":1641636147000},"page":"1434-1443","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Base Editing of Human Pluripotent Stem Cells for Modeling Long QT Syndrome"],"prefix":"10.1007","volume":"18","author":[{"given":"Fujian","family":"Wu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tianwei","family":"Guo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lixiang","family":"Sun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Furong","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6255-5181","authenticated-orcid":false,"given":"Xiaofei","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2022,1,8]]},"reference":[{"issue":"7570","key":"10324_CR1","doi-asserted-by":"publisher","first-page":"469","DOI":"10.1038\/nature15515","volume":"525","author":"A De Los Angeles","year":"2015","unstructured":"De Los Angeles, A., Ferrari, F., Xi, R., Fujiwara, Y., Benvenisty, N., Deng, H., Hochedlinger, K., Jaenisch, R., Lee, S., Leitch, H. 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(2021). iPSCs: A preclinical drug research tool for neurological disorders. International Journal of Molecular Sciences, 22(9), 4596.","journal-title":"International Journal of Molecular Sciences"},{"issue":"3","key":"10324_CR4","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1016\/j.stem.2015.08.017","volume":"17","author":"M Hicks","year":"2015","unstructured":"Hicks, M., & Pyle, A. (2015). The path from pluripotency to skeletal muscle: Developmental Myogenesis guides the way. Cell Stem Cell, 17(3), 255\u2013257.","journal-title":"Cell Stem Cell"},{"issue":"1","key":"10324_CR5","doi-asserted-by":"publisher","first-page":"672","DOI":"10.1038\/s41467-017-00668-4","volume":"8","author":"Y Shan","year":"2017","unstructured":"Shan, Y., Liang, Z., Xing, Q., Zhang, T., Wang, B., Tian, S., Huang, W., Zhang, Y., Yao, J., Zhu, Y., Huang, K., Liu, Y., Wang, X., Chen, Q., Zhang, J., Shang, B., Li, S., Shi, X., Liao, B., et al. (2017). PRC2 specifies ectoderm lineages and maintains pluripotency in primed but not na\u00efve ESCs. Nature Communications, 8(1), 672.","journal-title":"Nature Communications"},{"issue":"5","key":"10324_CR6","doi-asserted-by":"publisher","first-page":"861","DOI":"10.1016\/j.cell.2007.11.019","volume":"131","author":"K Takahashi","year":"2007","unstructured":"Takahashi, K., Tanabe, K., Ohnuki, M., Narita, M., Ichisaka, T., Tomoda, K., & Yamanaka, S. (2007). Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell., 131(5), 861\u2013872.","journal-title":"Cell."},{"issue":"8","key":"10324_CR7","doi-asserted-by":"publisher","first-page":"855","DOI":"10.1038\/nmeth.2999","volume":"11","author":"PW Burridge","year":"2014","unstructured":"Burridge, P. W., Matsa, E., Shukla, P., Lin, Z. C., Churko, J. M., Ebert, A. D., Lan, F., Diecke, S., Huber, B., Mordwinkin, N. M., Plews, J. R., Abilez, O. J., Cui, B., Gold, J. D., & Wu, J. C. (2014). 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