Electrophysiological Properties of Prion-Positive Cardiac Progenitors Derived From Murine Embryonic Stem Cells

• Fujii Hiroshi

  Division of Regenerative Medicine and Therapeutics, Institute of Regenerative Medicine and Biofunction, Tottori University Graduate School of Medical Science Division of Regenerative Medicine and Therapeutics, Institute of Regenerative Medicine and Biofunction, Tottori University Graduate School of Medical Science

• Ikeuchi Yu

  Division of Regenerative Medicine and Therapeutics, Institute of Regenerative Medicine and Biofunction, Tottori University Graduate School of Medical Science Division of Regenerative Medicine and Therapeutics, Institute of Regenerative Medicine and Biofunction, Tottori University Graduate School of Medical Science

• Kurata Yasutaka

  Department of Physiology II, Kanazawa Medical University Department of Physiology II, Kanazawa Medical University

• Ikeda Nobuhito

  Division of Regenerative Medicine and Therapeutics, Institute of Regenerative Medicine and Biofunction, Tottori University Graduate School of Medical Science Division of Regenerative Medicine and Therapeutics, Institute of Regenerative Medicine and Biofunction, Tottori University Graduate School of Medical Science

• Bahrudin Udin

  Division of Regenerative Medicine and Therapeutics, Institute of Regenerative Medicine and Biofunction, Tottori University Graduate School of Medical Science Division of Regenerative Medicine and Therapeutics, Institute of Regenerative Medicine and Biofunction, Tottori University Graduate School of Medical Science

• Li Peili

  Division of Regenerative Medicine and Therapeutics, Institute of Regenerative Medicine and Biofunction, Tottori University Graduate School of Medical Science Division of Regenerative Medicine and Therapeutics, Institute of Regenerative Medicine and Biofunction, Tottori University Graduate School of Medical Science

• Nakayama Yuji

  Division of Functional Genomics, Research Center for Bioscience and Technology, Tottori University Division of Functional Genomics, Research Center for Bioscience and Technology, Tottori University

• Endo Ryo

  Division of Regenerative Medicine and Therapeutics, Institute of Regenerative Medicine and Biofunction, Tottori University Graduate School of Medical Science Division of Regenerative Medicine and Therapeutics, Institute of Regenerative Medicine and Biofunction, Tottori University Graduate School of Medical Science

• Hasegawa Akira

  Division of Regenerative Medicine and Therapeutics, Institute of Regenerative Medicine and Biofunction, Tottori University Graduate School of Medical Science Division of Regenerative Medicine and Therapeutics, Institute of Regenerative Medicine and Biofunction, Tottori University Graduate School of Medical Science

• Morikawa Kumi

  Division of Regenerative Medicine and Therapeutics, Institute of Regenerative Medicine and Biofunction, Tottori University Graduate School of Medical Science Division of Regenerative Medicine and Therapeutics, Institute of Regenerative Medicine and Biofunction, Tottori University Graduate School of Medical Science

• Miake Junichiro

  Division of Cardiology, Tottori University Hospital Division of Cardiology, Tottori University Hospital

• Yoshida Akio

  Division of Regenerative Medicine and Therapeutics, Institute of Regenerative Medicine and Biofunction, Tottori University Graduate School of Medical Science Division of Regenerative Medicine and Therapeutics, Institute of Regenerative Medicine and Biofunction, Tottori University Graduate School of Medical Science

• Hidaka Kyoko

  Center for Fundamental Education, University of Kitakyushu Center for Fundamental Education, University of Kitakyushu

• Morisaki Takayuki

  Department of Bioscience and Genetics, National Cerebral and Cardiovascular Center Research Institute Department of Bioscience and Genetics, National Cerebral and Cardiovascular Center Research Institute

• Ninomiya Haruaki

  Department of Biological Regulation, Tottori University Faculty of Medicine Department of Biological Regulation, Tottori University Faculty of Medicine

• Shirayoshi Yasuaki

  Division of Regenerative Medicine and Therapeutics, Institute of Regenerative Medicine and Biofunction, Tottori University Graduate School of Medical Science Division of Regenerative Medicine and Therapeutics, Institute of Regenerative Medicine and Biofunction, Tottori University Graduate School of Medical Science

• Yamamoto Kazuhiro

  Division of Cardiology, Tottori University Hospital Division of Cardiology, Tottori University Hospital

• Hisatome Ichiro

  Division of Regenerative Medicine and Therapeutics, Institute of Regenerative Medicine and Biofunction, Tottori University Graduate School of Medical Science Division of Regenerative Medicine and Therapeutics, Institute of Regenerative Medicine and Biofunction, Tottori University Graduate School of Medical Science

抄録

Background: The prion protein (PrP) has been reported to serve as a surface maker for isolation of cardiomyogenic progenitors from murine embryonic stem (ES) cells. Although PrP-positive cells exhibited automaticity, their electrophysiological characteristics remain unresolved. The aim of the present study was therefore to investigate the electrophysiological properties of PrP-positive cells in comparison with those of HCN4p-or Nkx2.5-positive cells. Methods and Results: Differentiation of AB1, HCN5p-EGFP and hcgp7 ES cells into cardiac progenitors was induced by embryoid body (EB) formation. EBs were dissociated and cells expressing PrP, HCN4-EGFP and/or Nkx2.5-GFP were collected via flow cytometry. Sorted cells were subjected to reverse transcriptase-polymerase chain reaction, immunostaining and patch-clamp experiments. PrP-positive cells expressed mRNA of undifferentiation markers, first and second heart field markers, and cardiac-specific genes and ion channels, indicating their commitment to cardiomyogenic progenitors. PrP-positive cells with automaticity showed positive and negative chronotropic responses to isoproterenol and carbamylcholine, respectively. Hyperpolarization-activated cation current (I_f) was barely detectable, whereas Na⁺ and L-type Ca²⁺ channel currents were frequently observed. Their spontaneous activity was slowed by inhibition of sarcoplasmic reticulum Ca²⁺ uptake and release but not by blocking I_f. The maximum diastolic potential of their spontaneous firings was more depolarized than that of Nkx2.5-GFP-positive cells. Conclusions: PrP-positive cells contained cardiac progenitors that separated from the lineage of sinoatrial node cells. PrP can be used as a marker to enrich nascent cardiac progenitors.  (Circ J 2012; 76: 2875–2883)<br>

収録刊行物

• Circulation Journal

  Circulation Journal 76 (12), 2875-2883, 2012

  一般社団法人 日本循環器学会

キーワード

• Automaticity
• HCN4
• Murine embryonic stem cell
• Nkx2.5
• Prion protein

詳細情報

• CRID: 1390001205103091968
• NII論文ID: 10031126061
• NII書誌ID: AA11591968
• DOI: 10.1253/circj.cj-12-0126
• COI: 1:STN:280:DC%2BC38bmsVSjuw%3D%3D
• ISSN: 13474820
• ISSN: 13469843
• PubMed: 22972200
• Web Site: https://www.jstage.jst.go.jp/article/circj/76/12/76_CJ-12-0126/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/2013307028
• 本文言語コード: en
• データソース種別:
  • JaLC
  • Crossref
  • PubMed
  • CiNii Articles
  • KAKEN
• 抄録ライセンスフラグ: 使用不可