Tbx18 promoted the conversion of human-induced pluripotent stem cell-derived cardiomyocytes into sinoatrial node-like pacemaker cells.
Wei ZhangHongyi ZhaoDajun QuanYanhong TangXi WangCongxin HuangPublished in: Cell biology international (2021)
Sinoatrial node (SAN) pacemaker cells originate from Tbx18 (T-box transcription factor 18)-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, human-induced pluripotent stem cells (hiPSCs) were firstly 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 (HCN4), connexin (CX)-45 in the Tbx18-CMs group were markedly up-regulated, while the expressions of transcription factor NKX2.5, CX43 were significantly down-regulated. Whole-cell patch-clamp results illustrated that action potential (AP) and "funny" current (If ) 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. This article is protected by copyright. All rights reserved.
Keyphrases
- transcription factor
- induced pluripotent stem cells
- induced apoptosis
- endothelial cells
- cell cycle arrest
- high glucose
- cell proliferation
- dna binding
- stem cells
- signaling pathway
- pluripotent stem cells
- oxidative stress
- mesenchymal stem cells
- single cell
- poor prognosis
- diabetic rats
- climate change
- small molecule
- quantum dots
- long non coding rna
- bone marrow
- human health
- drug induced
- pi k akt
- single molecule
- vena cava