Tbx18 promoted the conversion of human‐induced pluripotent stem cell‐derived cardiomyocytes into sinoatrial node‐like pacemaker cells
Wei Zhang, Hongyi Zhao, Dajun Quan, Yanhong Tang, Xi Wang, Congxin Huang
Abstract
Abstract Sinoatrial node (SAN) pacemaker cells originate from T‐box transcription factor 18 (Tbx18)‐expressing progenitor cells. The present study aimed to investigate whether overexpression of human transcription factor Tbx18 could reprogram human‐induced pluripotent stem cell‐derived cardiomyocytes (hiPSC‐CMs) into SAN‐like pacemaker cells (SANLPCs) in vitro. In the study, hiPSCs were first differentiated into hiPSC‐CMs through regulating the Wnt/β‐catenin pathway, then purified hiPSC‐CMs were transfected by Tbx18 adenovirus (Tbx18‐CMs group) or green fluorescent protein (GFP) adenovirus (GFP‐CMs group). The beating frequency of the Tbx18‐CMs group was significantly higher than that of the hiPSC‐CMs group and GFP‐CMs group. Compared with the other two groups, the expression levels of hyperpolarization‐activated cyclic nucleotide‐gated potassium channel isoform 4, connexin‐45 in the Tbx18‐CMs group were markedly upregulated, while the expressions of transcription factor NKX2.5, CX43 were significantly downregulated. Whole‐cell patch‐clamp results illustrated that action potential and “funny” current ( I f ) similar to SAN pacemaker cells could be recorded in the Tbx18‐CMs group. In conclusion, this present study demonstrated that overexpression of Tbx18 promoted the conversion of hiPSC‐CMs into SANLPCs.