The text has been copied to the clipboard
Back
Full-text
Journal article

Notch pathway activation enhances cardiosphere in vitro expansion.

  • Secco I Molecular Medicine Laboratory, International Centre for Genetic Engineering and Biotechnology (ICGEB), Trieste, Italy.
  • Barile L Fondazione Cardiocentro Ticino and Swiss Institute for Regenerative Medicine, Lugano, Switzerland.
  • Torrini C Molecular Medicine Laboratory, International Centre for Genetic Engineering and Biotechnology (ICGEB), Trieste, Italy.
  • Zentilin L Molecular Medicine Laboratory, International Centre for Genetic Engineering and Biotechnology (ICGEB), Trieste, Italy.
  • Vassalli G Fondazione Cardiocentro Ticino and Swiss Institute for Regenerative Medicine, Lugano, Switzerland.
  • Giacca M Molecular Medicine Laboratory, International Centre for Genetic Engineering and Biotechnology (ICGEB), Trieste, Italy.
  • Collesi C Molecular Medicine Laboratory, International Centre for Genetic Engineering and Biotechnology (ICGEB), Trieste, Italy.
Show more…
  • 2018-08-24
Published in:
  • Journal of cellular and molecular medicine. - 2018
Adeno-associated virus (AAV)
Cardiac Progenitors
Micro-RNAs
Notch
Calcium-Binding Proteins
Cell Differentiation
Cell Proliferation
Cells, Cultured
Dependovirus
Gene Expression Regulation, Developmental
Genetic Vectors
Humans
Jagged-1 Protein
MicroRNAs
Myocytes, Cardiac
Receptor, Notch1
Signal Transduction
Transfection
English Cardiospheres (CSps) are self-assembling clusters of a heterogeneous population of poorly differentiated cells outgrowing from in vitro cultured cardiac explants. Scanty information is available on the molecular pathways regulating CSp growth and their differentiation potential towards cardiac and vascular lineages. Here we report that Notch1 stimulates a massive increase in both CSp number and size, inducing a peculiar gene expression programme leading to a cardiovascular molecular signature. These effects were further enhanced using Adeno-Associated Virus (AAV)-based gene transfer of activated Notch1-intracellular domain (N1-ICD) or soluble-Jagged1 (sJ1) ligand to CSp-forming cells. A peculiar effect was exploited by selected pro-proliferating miRNAs: hsa-miR-590-3p induced a cardiovascular gene expression programme, while hsa-miR-199a-3p acted as the most potent stimulus for the activation of the Notch pathway, thus showing that, unlike in adult cardiomyocytes, these miRNAs involve Notch signalling activation in CSps. Our results identify Notch1 as a crucial regulator of CSp growth and differentiation along the vascular lineage, raising the attracting possibility that forced activation of this pathway might be exploited to promote in vitro CSp expansion as a tool for toxicology screening and cell-free therapeutic strategies.
Language
  • English
Open access status
gold
Identifiers
Persistent URL
https://sonar.ch/global/documents/256499
Export to…
JSON data
Dublin Core
BibTeX
RIS (Zotero, …)
Statistics
Document views: 41 File downloads:
  • Full-text: 0