A dual SHOX2:GFP; MYH6:mCherry knockin hESC reporter line for derivation of human SAN-like cells.

TitleA dual SHOX2:GFP; MYH6:mCherry knockin hESC reporter line for derivation of human SAN-like cells.
Publication TypeJournal Article
Year of Publication2022
AuthorsGhazizadeh, Z, Zhu, J, Fattahi, F, Tang, A, Sun, X, Amin, S, Tsai, S-Y, Khalaj, M, Zhou, T, Samuel, RM, Zhang, T, Ortega, FA, Gordillo, M, Moroziewicz, D, Paull, D, Noggle, SA, Xiang, JZhaoying, Studer, L, Christini, DJ, Pitt, GS, Evans, T, Chen, S
Corporate AuthorsNYSCF Global Stem Cell Array® Team
JournaliScience
Volume25
Issue4
Pagination104153
Date Published2022 Apr 15
ISSN2589-0042
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.

DOI10.1016/j.isci.2022.104153
Alternate JournaliScience
PubMed ID35434558
PubMed Central IDPMC9010642