The method of sinus node-like pacemaker cells from human induced pluripotent stem cells by BMP and Wnt signaling

Wang, Fengyuan; Yin, Lu; Zhang, Wei; Tang, Yanhong; Wang, Xi; Huang, Congxin

doi:10.1007/s10565-023-09797-7

Cited by 3 publications

(2 citation statements)

References 45 publications

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“…Consistent with a previous study (Protze et al, 2017), compared with CON cardiomyocytes, hiPSC-CMs in the CDH5 group exhibited higher levels of pacemaker channel genes (HCN1, HCN4, and KCNJ3). Suppressing the endogenous inward rectifier potassium current (I K1 ) was first used to create biological pacemaker via gene therapy (Cingolani et al, 2018) In contrast to prior investigations (Gharibeh et al, 2021;Liu et al, 2020;Protze et al, 2017;Wang et al, 2023;Yin et al, 2022;Zhang et al, 2022;Zhao, Wang, et al, 2020), our approach to procuring SANLPCs exhibits superior attributes in terms of simplicity, controllability, and cost-effectiveness. However, in relation to the final proportion of acquired SANLPCs, our study did not present a notable advantage compared with previous research (Liang et al, 2020;Ren et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

“…SANLPCs exhibit the expression of cTNT while not expressing the transcription factor NKX2.5 (Protze et al, 2017). In contrast, working cardiomyocytes display high levels of cTNT and NKX2.5 expression (Protze et al, 2017;Wang et al, 2023). These distinctive expression patterns serve as reliable markers to distinguish SANLPCs from working cardiomyocytes.…”

Section: Cdh5 Provoked a Notable Increase In The Proportion Of Sanlpc...mentioning

confidence: 99%

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Cadherin‐5 facilitated the differentiation of human induced pluripotent stem cells into sinoatrial node‐like pacemaker cells by regulating β‐catenin

Zhang,

Wang,

Yin

et al. 2023

Journal Cellular Physiology

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Our study was conducted to investigate whether cadherin‐5 (CDH5), a vascular endothelial cell adhesion glycoprotein, could facilitate the differentiation of human induced pluripotent stem cells (hiPSCs) into sinoatrial node‐like pacemaker cells (SANLPCs), following previous findings of silk‐fibroin hydrogel‐induced direct conversion of quiescent cardiomyocytes into pacemaker cells in rats through the activation of CDH5. In this study, the differentiating hiPSCs were treated with CDH5 (40 ng/mL) between Day 5 and 7 during cardiomyocytes differentiation. The findings in the present study demonstrated that CDH5 stimulated the expression of pacemaker‐specific markers while suppressing markers associated with working cardiomyocytes, resulting in an increased proportion of SANLPCs among hiPSCs‐derived cardiomyocytes (hiPSC‐CMs) population. Moreover, CDH5 induced typical electrophysiological characteristics resembling cardiac pacemaker cells in hiPSC‐CMs. Further mechanistic investigations revealed that the enriched differentiation of hiPSCs into SANLPCs induced by CDH5 was partially reversed by iCRT14, an inhibitor of β‐catenin. Therefore, based on the aforementioned findings, it could be inferred that the regulation of β‐catenin by CDH5 played a crucial role in promoting the enriched differentiation of hiPSCs into SANLPCs, which presents a novel avenue for the construction of biological pacemakers in forthcoming research.

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Section: Discussionmentioning

confidence: 99%

Section: Cdh5 Provoked a Notable Increase In The Proportion Of Sanlpc...mentioning

confidence: 99%

Cadherin‐5 facilitated the differentiation of human induced pluripotent stem cells into sinoatrial node‐like pacemaker cells by regulating β‐catenin

Zhang,

Wang,

Yin

et al. 2023

Journal Cellular Physiology

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Evaluation of the Potential Targets of Shenxian–Shengmai Oral Liquid in Treating Sick Sinus Syndrome Based on Network Pharmacology and Molecular Docking

Hou,

Zhang,

Min

et al. 2024

Food Science & Nutrition

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Shenxian–Shengmai (SXSM) is a Chinese patent medicine used in the treatment of sick sinus syndrome (SSS). However, its active chemical compounds and the underlying molecular mechanisms remain unclear. In this study, we researched the underlying mechanisms of SXSM in treating SSS. We conducted network analysis and molecular docking to identify the small molecules and core targets responsible for the therapeutic efficacy of SXSM on SSS. In vitro experiments were performed to verify the potential therapeutic mechanism. Network pharmacological analysis identified 17 core targets. Among these, BMP4, KCNH2, KCNMA1, and KCNQ1 were identified to be involved in various biological processes, such as the formation and regulation of the cardiac pacemaking system and potassium ion transmembrane transport. The experimental analysis revealed that SXSM could upregulate the expression of the Bmp4/Tbx3/Hcn4 pathway and the expression of Kcnh2, Kcnma1, and Kcnq1 channels, which protected and improved the pacemaking function of pacemaker cells (P cells) and increased the heart rate. These findings provide a scientific basis in the study of the mechanism of traditional Chinese medicine in the treatment of SSS.

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Efficient generation of TBX3+ atrioventricular conduction-like cardiomyocytes from human pluripotent stem cells

Bai

Zhao

2023

Biochemical and Biophysical Research Communications

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The method of sinus node-like pacemaker cells from human induced pluripotent stem cells by BMP and Wnt signaling

Cited by 3 publications

References 45 publications

Cadherin‐5 facilitated the differentiation of human induced pluripotent stem cells into sinoatrial node‐like pacemaker cells by regulating β‐catenin

Cadherin‐5 facilitated the differentiation of human induced pluripotent stem cells into sinoatrial node‐like pacemaker cells by regulating β‐catenin

Evaluation of the Potential Targets of Shenxian–Shengmai Oral Liquid in Treating Sick Sinus Syndrome Based on Network Pharmacology and Molecular Docking

Efficient generation of TBX3+ atrioventricular conduction-like cardiomyocytes from human pluripotent stem cells

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