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, ⁎ Benvenuto su EM|consulte, il riferimento dei professionisti della salute.
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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.
Il testo completo di questo articolo è disponibile in PDF.Keywords : TBX3, Human induced pluripotent stem cell (hiPSCs), Pacemaker-like cells
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Vol 130
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