CD151 expression indicates the subtype specification of human induced pluripotent stem cell-derived atrial and ventricular cardiomyocytes

Current differentiation protocols for human pluripotent stem cells produce a heterogeneous population of cardiomyocytes (CMs). Here, we identified CD151 as a marker of ventricular CMs (VCMs) and atrial CMs (ACMs) from 212 different cell surface markers. In the VCM induction, CD151high CMs were a homogeneous population of mature VCMs, including binuclear VCMs, and showed enriched cell cycle-related genes based on RNA-seq analysis. As for the ACM induction, CD151low CMs expressed high levels of atrial-related genes and exhibited atrial-type electrophysiological properties. According to RNA-seq analysis, CD151high CMs from the ACM induction had molecular signatures for cell-cell interactions and NOTCH signaling. When treated with a NOTCH signal inhibitor, the same cells showed mature electrophysiological properties consistent of ACMs with an increasing expression of atrial-related genes. Altogether, we found that CD151 is an indicator of subtype specification with distinct mechanisms between VCM and ACM differentiation and that NOTCH signaling inhibition enhances atrial specification. mRNA profiles of hiPSC-CMs sorted by CD151 were generated by deep sequencing, in triplicate, using Illumina Nextseq 500.