Fluorescent reporter lines in human iPS cells offer useful platforms to study cardiac subtype specification, cell-based therapies of cardiac disease and drug development.

2016 Fiscal Year Final Research Report

• Project/Area Number: 26501003
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Regenerative medicine
• Research Institution: Tottori University
• Principal Investigator: Shirayoshi Yasuaki 鳥取大学, 医学(系)研究科(研究院), 准教授 (90249946)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: ヒトES細胞 / ヒトiPS細胞 / イオンチャネル / 蛍光タンパク質 / 心筋分化 / 再生医療 / ペースメーカ細部

Outline of Final Research Achievements

In order to use human ES/iPS cells in the fields of regenerative medicine and drug development, it is crucial to identify functionally distinct cardiac subtypes and to study their functional aspects in healthy and diseased conditions. To isolate nodal pacemaker cells and ventricular cardiomyocytes, we have established the dual cardiac fluorescent reporter human ES/iPS cells, in which HCN4 ion channel and MLC2v myosin light chain genes are knocked in with eGFP and mCherry, respectively.
Isolated HCN4-eGFP-positive (HCN4+) cells expressed endogenous HCN4 and exhibited action potential characteristic of a nodal-phenotype including If current. Using imaging techniques, we demonstrated that HCN4+ cells established electrical coupling with HL-1 atrial CMs. These results demonstrated the potential of human ES/iPS cells-derived HCN4+ cells to act as a rate-responsive biological pacemaker.

Free Research Field

幹細胞生物学