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标题：A dual SHOX2:GFP; MYH6:mCherry knockin hESC reporter line for derivation of human SAN-like cells
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作者：Zaniar Ghazizadeh ; Jiajun Zhu ; Faranak Fattahi 等
期刊名称：iScience
印刷版ISSN：2589-0042
出版年度：2022
卷号：25
期号：4
页码：1-19
DOI：10.1016/j.isci.2022.104153
语种：English
出版社：Elsevier
摘要：SummaryThe sinoatrial node (SAN) is the primary pacemaker of the heart. The human SAN is poorly understood due to limited primary tissue access and limitations in robustin vitroderivation methods. We developed a dualSHOX2:GFP; MYH6:mCherryknockin human embryonic stem cell (hESC) reporter line, which allows the identification and purification of SAN-like cells. Using this line, we performed several rounds of chemical screens and developed an efficient strategy to generate and purify hESC-derived SAN-like cells (hESC-SAN). The derived hESC-SAN cells display molecular and electrophysiological characteristics of bona fide nodal cells, which allowed exploration of their transcriptional profile at single-cell level. In sum, our dual reporter system facilitated an effective strategy for deriving human SAN-like cells, which can potentially be used for future disease modeling and drug discovery.Graphical abstractDisplay OmittedHighlights•We developed a dualSHOX2:GFP;MYH6:mCherryknockin hESC reporter line•An efficient strategy was developed to generate and purify hESC-SAN cells•hESC-SAN cells display molecular and electrophysiological identities of nodal cells•Single-cell RNA sequencing analysis was applied to characterize the hESC-SAN cellsBiological sciences; Stem cells research; Methodology in biological sciences