Overexpression of TBX3 in human induced pluripotent stem cells (hiPSCs) increases their differentiation into cardiac pacemaker-like cells
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 ca...
Main Authors: | , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Elsevier
2020-10-01
|
Series: | Biomedicine & Pharmacotherapy |
Subjects: | |
Online Access: | http://www.sciencedirect.com/science/article/pii/S0753332220308052 |
id |
doaj-6e9546f32f7248f081adf274ebc87aff |
---|---|
record_format |
Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Hongyi Zhao Fengyuan Wang Wei Zhang Mei Yang Yanhong Tang Xi Wang Qingyan Zhao Congxin Huang |
spellingShingle |
Hongyi Zhao Fengyuan Wang Wei Zhang Mei Yang Yanhong Tang Xi Wang Qingyan Zhao Congxin Huang Overexpression of TBX3 in human induced pluripotent stem cells (hiPSCs) increases their differentiation into cardiac pacemaker-like cells Biomedicine & Pharmacotherapy TBX3 Human induced pluripotent stem cell (hiPSCs) Pacemaker-like cells |
author_facet |
Hongyi Zhao Fengyuan Wang Wei Zhang Mei Yang Yanhong Tang Xi Wang Qingyan Zhao Congxin Huang |
author_sort |
Hongyi Zhao |
title |
Overexpression of TBX3 in human induced pluripotent stem cells (hiPSCs) increases their differentiation into cardiac pacemaker-like cells |
title_short |
Overexpression of TBX3 in human induced pluripotent stem cells (hiPSCs) increases their differentiation into cardiac pacemaker-like cells |
title_full |
Overexpression of TBX3 in human induced pluripotent stem cells (hiPSCs) increases their differentiation into cardiac pacemaker-like cells |
title_fullStr |
Overexpression of TBX3 in human induced pluripotent stem cells (hiPSCs) increases their differentiation into cardiac pacemaker-like cells |
title_full_unstemmed |
Overexpression of TBX3 in human induced pluripotent stem cells (hiPSCs) increases their differentiation into cardiac pacemaker-like cells |
title_sort |
overexpression of tbx3 in human induced pluripotent stem cells (hipscs) increases their differentiation into cardiac pacemaker-like cells |
publisher |
Elsevier |
series |
Biomedicine & Pharmacotherapy |
issn |
0753-3322 |
publishDate |
2020-10-01 |
description |
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. |
topic |
TBX3 Human induced pluripotent stem cell (hiPSCs) Pacemaker-like cells |
url |
http://www.sciencedirect.com/science/article/pii/S0753332220308052 |
work_keys_str_mv |
AT hongyizhao overexpressionoftbx3inhumaninducedpluripotentstemcellshipscsincreasestheirdifferentiationintocardiacpacemakerlikecells AT fengyuanwang overexpressionoftbx3inhumaninducedpluripotentstemcellshipscsincreasestheirdifferentiationintocardiacpacemakerlikecells AT weizhang overexpressionoftbx3inhumaninducedpluripotentstemcellshipscsincreasestheirdifferentiationintocardiacpacemakerlikecells AT meiyang overexpressionoftbx3inhumaninducedpluripotentstemcellshipscsincreasestheirdifferentiationintocardiacpacemakerlikecells AT yanhongtang overexpressionoftbx3inhumaninducedpluripotentstemcellshipscsincreasestheirdifferentiationintocardiacpacemakerlikecells AT xiwang overexpressionoftbx3inhumaninducedpluripotentstemcellshipscsincreasestheirdifferentiationintocardiacpacemakerlikecells AT qingyanzhao overexpressionoftbx3inhumaninducedpluripotentstemcellshipscsincreasestheirdifferentiationintocardiacpacemakerlikecells AT congxinhuang overexpressionoftbx3inhumaninducedpluripotentstemcellshipscsincreasestheirdifferentiationintocardiacpacemakerlikecells |
_version_ |
1721434775192862720 |
spelling |
doaj-6e9546f32f7248f081adf274ebc87aff2021-05-20T07:43:31ZengElsevierBiomedicine & Pharmacotherapy0753-33222020-10-01130110612Overexpression of TBX3 in human induced pluripotent stem cells (hiPSCs) increases their differentiation into cardiac pacemaker-like cellsHongyi Zhao0Fengyuan Wang1Wei Zhang2Mei Yang3Yanhong Tang4Xi Wang5Qingyan Zhao6Congxin Huang7Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, 430060, PR China; Cardiovascular Research Institute, Wuhan University, Wuhan, 430060, PR China; Hubei Key Laboratory of Cardiology, Wuhan, 430060, PR ChinaDepartment of Cardiology, Renmin Hospital of Wuhan University, Wuhan, 430060, PR China; Cardiovascular Research Institute, Wuhan University, Wuhan, 430060, PR China; Hubei Key Laboratory of Cardiology, Wuhan, 430060, PR ChinaDepartment of Cardiology, Renmin Hospital of Wuhan University, Wuhan, 430060, PR China; Cardiovascular Research Institute, Wuhan University, Wuhan, 430060, PR China; Hubei Key Laboratory of Cardiology, Wuhan, 430060, PR ChinaDepartment of Cardiology, Renmin Hospital of Wuhan University, Wuhan, 430060, PR China; Cardiovascular Research Institute, Wuhan University, Wuhan, 430060, PR China; Hubei Key Laboratory of Cardiology, Wuhan, 430060, PR ChinaDepartment of Cardiology, Renmin Hospital of Wuhan University, Wuhan, 430060, PR China; Cardiovascular Research Institute, Wuhan University, Wuhan, 430060, PR China; Hubei Key Laboratory of Cardiology, Wuhan, 430060, PR ChinaDepartment of Cardiology, Renmin Hospital of Wuhan University, Wuhan, 430060, PR China; Cardiovascular Research Institute, Wuhan University, Wuhan, 430060, PR China; Hubei Key Laboratory of Cardiology, Wuhan, 430060, PR ChinaDepartment of Cardiology, Renmin Hospital of Wuhan University, Wuhan, 430060, PR China; Cardiovascular Research Institute, Wuhan University, Wuhan, 430060, PR China; Hubei Key Laboratory of Cardiology, Wuhan, 430060, PR China; Correspondin authors at: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, 430060, PR China.Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, 430060, PR China; Cardiovascular Research Institute, Wuhan University, Wuhan, 430060, PR China; Hubei Key Laboratory of Cardiology, Wuhan, 430060, PR China; Correspondin authors at: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, 430060, PR China.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.http://www.sciencedirect.com/science/article/pii/S0753332220308052TBX3Human induced pluripotent stem cell (hiPSCs)Pacemaker-like cells |