Higher cardiogenic potential of IPSCs derived from cardiac versus skin stromal cells

Viviana Meraviglia, Jianyan Wen, Luca Piacentini, Giulia Campostrini, Cheng Wang, Maria Cristina Florio, Valerio Azzimato, Lorenzo Fassina, Martin Langes, Johnson Wong, Michele Miragoli, Carlo Gaetano, Giulio Pompilio, Andrea Barbuti, Dario DiFrancesco, Deborah Mascalzoni, Peter P. Pramstaller, Gualtiero I. Colombo, Huei Sheng Vincent Chen, Alessandra Rossini

Research output: Contribution to journalArticlepeer-review

Abstract

Prior studies have demonstrated that founder cell type could influence induced pluripotent stem cells (iPSCs) molecular and developmental properties at early passages after establishing their pluripotent state. Herein, we evaluated the persistence of a functional memory related to the tissue of origin in iPSCs from syngeneic cardiac (CStC) vs skin stromal cells (SStCs). We found that, at passages greater than 15, iPSCs from cardiac stromal cells (C-iPSCs) produced a higher number of beating embryoid bodies than iPSCs from skin stromal cells (S-iPSCs). Flow cytometry analysis revealed that dissected beating areas from C-iPSCs exhibited more Troponin-T positive cells compared to S-iPSCs. Beating areas derived from C-iPSCs displayed higher expression of cardiac markers, more hyperpolarized diastolic potentials, larger action potential amplitude and higher contractility than beaters from skin. Also, different microRNA subsets were differentially modulated in CStCs vs SStCs during the reprogramming process, potentially accounting for the higher cardiogenic potentials of C-iPSCs vs S-iPSCs. Therefore, the present work supports the existence of a founder organ memory in iPSCs obtained from the stromal component of the origin tissue.

Original languageEnglish
Pages (from-to)719-743
Number of pages25
JournalFrontiers in Bioscience
Volume21
Issue number4
Publication statusPublished - Jan 1 2016

Keywords

  • Cardiomyocytes
  • Cardiomyogenic differentiation
  • Fibroblasts
  • Induced pluripotent stem cells
  • Stromal cells

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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