Stem Cell Res Ther
Department of Cardiology, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuchang, Wuhan, 430060, Hubei, People's Republic of China.
Published: July 2022
Background: The source of SAN is debated among researchers. Many studies have shown that RA and Wnt signaling are involved in heart development. In this study, we investigated the role of retinoic acid (RA) and Wnt signaling in the induction of sinus node-like cells.
Methods: The experimental samples were divided into four groups: control group (CHIR = 0), CHIR = 3, RA + CHIR = 0 andRA + CHIR = 3. After 20 days of differentiation, Western blot, RT-qPCR, immunofluorescence and flow cytometry were performed to identify sinus node-like cells. Finally, whole-cell patch clamp technique was used to record pacing funny current and action potential (AP) in four groups.
Results: The best intervention method used in our experiment was RA = 0.25 µmol/L D5-D9 + CHIR = 3 µmol/L D5-D7. Results showed that CHIR can increase the expression of ISL-1 and TBX3, while RA mainly elevated Shox2. Immunofluorescence assay and flow cytometry further illustrated that combining RA with CHIR can induce sinus node-like cells (CTNTShox2Nkx2.5). Moreover, CHIR might reduce the frequency of cell beats, but in conjunction with RA could partly compensate for this side effect. Whole cell patch clamps were able to record funny current and the typical sinus node AP in the experimental group, which did not appear in the control group.
Conclusions: Combining RA with Wnt signaling within a specific period can induce sinus node-like cells.
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http://dx.doi.org/10.1186/s13287-022-03006-8 | DOI Listing |
Nat Commun
November 2024
McEwen Stem Cell Institute, University Health Network, Toronto, ON, Canada.
The sinoatrial node regulates the heart rate throughout life. Failure of this primary pacemaker results in life-threatening, slow heart rhythm. Despite its critical function, the cellular and molecular composition of the human sinoatrial node is not resolved.
View Article and Find Full Text PDFCell Biol Toxicol
December 2023
Department of Cardiology, Renmin Hospital of Wuhan University, Cardiovascular Research Institute, Wuhan University, Hubei Key Laboratory of Cardiology, 238 Jiefang Road, Wuchang, Wuhan, Hubei, 430060, People's Republic of China.
The embryonic development of sinus nodes (SAN) is co-regulated by multiple signaling pathways. Among these, the bone morphogenetic protein (BMP) and Wnt signaling pathways are involved in the development of SAN. In this study, the effects of BMP and Wnt signaling on the differentiation of SAN-like pacemaker cells (SANLPCs) were investigated.
View Article and Find Full Text PDFRev Cardiovasc Med
November 2022
Department of Cardiovascular Medicine, Gunma University Graduate School of Medicine, Maebashi, 371-8511 Gunma, Japan.
Our understanding of the variants of slow pathway (SP) and associated atypical atrioventricular (AV) nodal reentrant tachycardia (NRT) is still growing. We have identified variants extending outside Koch's triangle along the tricuspid annulus, including superior, superoanterior and inferolateral right atrial SP and associated atypical, fast-slow AVNRT. We review the history of each variant, their electrophysiological characteristics and related atypical AVNRT, and their treatment by catheter ablation.
View Article and Find Full Text PDFStem Cell Res Ther
July 2022
Department of Cardiology, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuchang, Wuhan, 430060, Hubei, People's Republic of China.
Background: The source of SAN is debated among researchers. Many studies have shown that RA and Wnt signaling are involved in heart development. In this study, we investigated the role of retinoic acid (RA) and Wnt signaling in the induction of sinus node-like cells.
View Article and Find Full Text PDFStem Cell Res Ther
July 2020
Department of Cardiac Macrovascular Surgery, Affiliated Hospital of Southwest Medical University, 3-319 Zhongshan Road, Luzhou, 646000, Sichuan, China.
Background: Biological pacemakers derived from pluripotent stem cell (PSC) have been considered as a potential therapeutic surrogate for sick sinus syndrome. So it is essential to develop highly efficient strategies for enrichment of sinoatrial node-like cells (SANLCs) as seed cells for biological pacemakers. It has been reported that BMP, FGF, and RA signaling pathways are involved in specification of different cardiomyocyte subtypes, pacemaker, ventricular, and atrial cells.
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