Title:Roadmap to Cellular Reprogramming – Manipulating Transcriptional Networks with DNA, RNA, Proteins and Small Molecules
VOLUME: 13 ISSUE: 5
Author(s):P. Worsdorfer, M. Thier, A. Kadari and F. Edenhofer
Affiliation:Stem Cell Engineering Group, Institute of Reconstructive Neurobiology, University of Bonn - Life & Brain Center and Hertie Foundation, Sigmund-Freud Strasse 25, D-53105 Bonn, Germany.
Keywords:Cell lineage conversion, cell-penetrating peptide, cre/loxP recombination, factor-free iPS cell, protein
transduction, reprogramming, small molecule, transposon, viral transduction.
Abstract:Recent reports demonstrate that the plasticity of mammalian somatic cells is much higher than
previously assumed and that ectopic expression of transcription factors may have the potential to induce the
conversion of any cell type into another. Fibroblast cells can be converted into embryonic stem cell-like cells,
neural cells, cardiomyocytes, macrophage-like cells as well as blood progenitors. Additionally, the conversion
of astrocytes into neurons or neural stem cells into monocytes has been demonstrated. Nowadays, in the era
of systems biology, continuously growing holistic data sets are providing increasing insights into core
transcriptional networks and cellular signaling pathways. This knowledge enables cell biologists to understand
how cellular fate is determined and how it could be manipulated. As a consequence for biomedical
applications, it might be soon possible to convert patient specific somatic cells directly into desired
transplantable other cell types. The clinical value, however, of such reprogrammed cells is currently limited due
to the invasiveness of methods applied to induce reprogramming factor activity. This review will focus on
experimental strategies to ectopically induce cell fate modulators. We will emphasize those strategies that
enable efficient and robust overexpression of transcription factors by minimal genetic alterations of the host
genome. Furthermore, we will discuss procedures devoid of any genomic manipulation, such as the direct
delivery of mRNA, proteins, or the use of small molecules. By this, we aim to give a comprehensive overview
on state of the art techniques that harbor the potential to generate safe reprogrammed cells for clinical
applications.
