Overexpression of TBX3 in human induced pluripotent stem cells (hiPSCs) increases their differentiation into cardiac pacemaker-like cells - 27/10/20
, Congxin Huang a, b, c, ⁎ Bienvenue sur EM-consulte, la référence des professionnels de santé.
L’accès au texte intégral de cet article nécessite un abonnement.
| pages | 9 |
| Iconographies | 9 |
| Vidéos | 0 |
| Autres | 0 |
Highlights |
• | TBX3 regulates the development of the sinoatrial node in embryonic development. |
• | Overexpression of TBX3 in hiPSCs increases the differentiation of pacemaker cells. |
• | 3.TBX3 resulted in upregulation of pacemaker specific gene and ion channels expression. |
• | TBX3 can be used as a potential factor to construct a biological pacemaker. |
Abstract |
Backgroud |
The TBX3(T-box 3)transcription factor is considered as an essential factor in sinoatrial node formation. While the effect of TBX3 in the differentiation of sinoatrial node cells from embryonic stem cells(ESCs) has been recognized, its role in human induced pluripotent stem cell derived cardiomyocytes(hiPSCMs) has not been addressed. Therefore, the purpose of the present study was to investigate whether overexpression of TBX3 in hiPSCs could increase their differentiation into pacemaker-like cells.
Methods |
The hiPSCs were transfected with TBX3 gene during differentiation into cardiomyocytes(CMs). The hiPSCMs were analyzed using immunofluorescence, RT-qPCR, flow cytometry, whole-cell patch clamp recording to identify the differentiation effect exerted by TBX3. We discovered that hiPSCs transfected with TBX3 showed more proportions of NKX2.5-cTNT + sinoatrial node cells and faster contracting rates.
Results |
The results showed increment in transcription factor TBX18, SHOX2; hyperpolarization-activated cyclic nucleotide (HCN) channel: HCN1, HCN2, HCN4, connexin 45(CX45), Na + Ca2+ exchanger(NCX) in TBX3 transfected hiPSCMs. Sinoatrial node cell specific If current and action potential were also confirmed by patch clamp in TBX3 transfected hiPSCMs and the pacemaker-like cells were able to pace hiPSCMs ex vivo.
Conclusion |
In conclusion, the present study demonstrated that overexpression of TBX3 could increase the differentiation of hiPSCs into pacemaker-like cells. Our study provide new strategy to construct a biological pacemaker, however, further study is still needed to identify the efficacy and safety of using the pacemaker-like cells to produce biological pacemaker in vivo.
Le texte complet de cet article est disponible en PDF.Keywords : TBX3, Human induced pluripotent stem cell (hiPSCs), Pacemaker-like cells
Plan
Vol 130
Article 110612- octobre 2020 Retour au numéro
Article précédent
- Acute metformin treatment provides cardioprotection via improved mitochondrial function in cardiac ischemia / reperfusion injury
- Siripong Palee, Louis Higgins, Tom Leech, Siriporn C. Chattipakorn, Nipon Chattipakorn
- Prolonged caffeine intake decreases alveolar bone damage induced by binge-like ethanol consumption in adolescent female rats
- Cristiane Maia, Bruno Gonçalves Pinheiro, Carla Cristiane Soares da Silva, Rodrigo A. Cunha, Deiweson Souza-Monteiro, Maria Karolina Martins Ferreira, Tuany Rafaeli Schmidt, Gabriela de Souza Balbinot, Fabrício Mezzomo Collares, Manoela Domingues Martins, Rafael Rodrigues Lima
Bienvenue sur EM-consulte, la référence des professionnels de santé.
L’accès au texte intégral de cet article nécessite un abonnement.
Bienvenue sur EM-consulte, la référence des professionnels de santé.
L’achat d’article à l’unité est indisponible à l’heure actuelle.
Déjà abonné à cette revue ?