A dual SHOX2:GFP; MYH6:mCherry knockin hESC reporter line for derivation of human SAN-like cells
Journal
iScience
Journal Volume
25
Journal Issue
4
Pages
104153
Date Issued
2022-04-15
Author(s)
Ghazizadeh, Zaniar
Zhu, Jiajun
Fattahi, Faranak
Tang, Alice
Sun, Xiaolu
Amin, Sadaf
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
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.
Subjects
Biological sciences | Methodology in biological sciences | Stem cells research
SDGs
Publisher
Elsevier Inc.
Type
journal article