Conversion of pericytes to neurons: a new guest at the reprogramming convention

Emmanuel Nivet,Juan Carlos Izpisua Belmonte,Ignacio Sancho-Martinez

doi:10.1186/scrt150

Abstract

Reprogramming strategies allow for the generation of virtually any cell type of the human body, which could be useful for cell-based therapy. Among the different reprogramming technologies available, direct lineage conversion offers the possibility to change the phenotype of a cell type to another one without pushing cells backwards to a plastic/proliferative stage. This approach has raised the possibility to apply a similar process in vivo in order to compensate for functional cell loss. Historically, the cerebral tissue is a prime choice for developing cell-based treatments. As local pericyte accumulation is observed after central nervous system injury, it can be reasoned that this cell type might be a good candidate for the conversion into new neurons in vivo. In this article, and by focusing on recent observations from Karow and colleagues demonstrating the possibility to convert human brain-derived pericytes into functional neurons, we present a brief overview of the state of the art and attempt to offer perspective as to how these interesting laboratory findings could be translated in the clinic.

Highlights

Reprogramming strategies allow for the generation of virtually any cell type of the human body, which could be useful for cell-based therapy
Numerous cocktails of transcription factor (TF) have to date been identified for the conversion of somatic cells all the way back to pluripotency or into more specialized cell types
By combining pluripotency-associated reprogramming factors with neural specifiers or defined media, other laboratories have reported that it is feasible to convert fibroblasts into expandable neural stem cells [6]. From these and other reports, two main lineage conversion strategies can be envisaged for clinical applications: the generation of the desired cell type(s) in vitro and its further transplantation; and the local in vivo conversion of one cell type into the one(s) required, in a similar way to what has been experimentally done with pancreatic cells

Summary

Introduction

Reprogramming strategies allow for the generation of virtually any cell type of the human body, which could be useful for cell-based therapy. Over the past 60 years, from the first nuclear transfer experiment to the description of cell fate conversions by forced expression/inhibition of cell-type specific transcription factors (TFs) and/or miRNAs, a great deal of evidence showing cell identity switches has been accumulated [1]. Numerous cocktails of TFs have to date been identified for the conversion of somatic cells all the way back to pluripotency or into more specialized cell types.

Results

Conclusion