Nuclear reprogramming strategy modulates differentiation potential of induced pluripotent stem cells

Almudena Martinez-Fernandez, Timothy J. Nelson, Andre Terzic

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

Bioengineered by ectopic expression of stemness factors, induced pluripotent stem (iPS) cells demonstrate embryonic stemcell-like properties and offer a unique platform for derivation of autologous pluripotent cells from somatic tissue sources. In the process of nuclear reprogramming, somatic tissues are converted to a pluripotent ground state, thus unlocking an unlimited potential to expand progenitor pools. Molecular dissection of nuclear reprogramming suggests that a residual memory derived from the original parental source, along with the remnants of the reprogramming process itself, leads to a biased potential of the bioengineered progeny to differentiate into target tissues such as cardiac cytotypes. In this way, iPS cells that fulfill pluripotency criteria may display heterogeneous profiles for lineage specification. Small molecule-based strategies have been identified that modulate the epigenetic state of reprogrammed cells and are optimized to erase the residual memory and homogenize the differentiation potential of iPS cells derived from distinct backgrounds. Here, we describe the salient components of the reprogramming process and their effect on the downstream differentiation capacity of the iPS populations in the context of cardiovascular regenerative applications.

Original languageEnglish (US)
Pages (from-to)131-137
Number of pages7
JournalJournal of cardiovascular translational research
Volume4
Issue number2
DOIs
StatePublished - Apr 2011

Keywords

  • Differentiation capacity
  • Epigenetic memory
  • Memory-free pluripotency
  • iPS

ASJC Scopus subject areas

  • Molecular Medicine
  • Genetics
  • Pharmaceutical Science
  • Cardiology and Cardiovascular Medicine
  • Genetics(clinical)

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