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A dual SHOX2:GFP; MYH6:mCherry knockin hESC reporter line for derivation of human SAN-like cells
Ghazizadeh, Zaniar; Zhu, Jiajun; Fattahi, Faranak; Tang, Alice; Sun, Xiaolu; Amin, Sadaf; Tsai, Su-Yi; Khalaj, Mona; Zhou, Ting; Samuel, Ryan M.; Zhang, Tuo; Ortega, Francis A.; Gordillo, Miriam; Moroziewicz, Dorota; Paull, Daniel; Noggle, Scott A.; Xiang, Jenny Zhaoying; Studer, Lorenz; Christini, David J.; Pitt, Geoffrey S.; Evans, Todd; Chen, Shuibing
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iScience
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2022-04-15
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25
Publication Issue
4
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104153
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PIIS2589004222004230.pdf
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Abstract
The 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 robust in vitro derivation methods. We developed a dual SHOX2:GFP; MYH6:mCherry knockin 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.
Citation
Ghazizadeh Z, Zhu J, Fattahi F, Tang A, Sun X, Amin S, Tsai SY, Khalaj M, Zhou T, Samuel RM, Zhang T, Ortega FA, Gordillo M, Moroziewicz D; NYSCF Global Stem Cell Array® Team; Paull D, Noggle SA, Xiang JZ, Studer L, Christini DJ, Pitt GS, Evans T, Chen S. A dual SHOX2:GFP; MYH6:mCherry knockin hESC reporter line for derivation of human SAN-like cells. iScience. 2022 Mar 25;25(4):104153. doi: 10.1016/j.isci.2022.104153. PMID: 35434558; PMCID: PMC9010642.