The dynamic stem cell microenvironment is orchestrated by microvesicle-mediated transfer of genetic information

Abstract

It has been commonly supposed that adultstem cells co-localize with supporting cells withinspecific regions or specialized microenvironment in eachtissue/organ, called stem cell niche. This concept wasbased on the assumption that stem cells are intrinsicallyhierarchical in nature. However, recent data indicate thatstem cells may represent a continuum with reversiblealterations in phenotype taking place during the transitthrough cell cycle. Based on this dynamic interpretationit has been suggested that the so-called niche isrepresented by a single or only few cell types continuallyadjusting their phenotype and function to individualcircumstances. A critical component in the regulation ofthe continuum of stem cell phenotypes is themicroenvironment. In this context, microvesicles (MVs)account for the transfer of genetic information betweencells. Originally considered inert cellular debris, MVsare increasingly recognized to be important mediators ofcell-to-cell communication. MVs may transfer receptors,proteins, mRNA and microRNA to target cells viaspecific receptor-mediated interaction. In stem cellbiology the exchange of genetic information may bebidirectional from stromal to stem cells. In the context oftissue injury the MV-mediated transfer of geneticinformation may reprogram the phenotype of stem cellsto acquire features of the injured tissue cells. In addition,MVs derived from stem cells may induce de-differentiation of cells which have survived injury with acell cycle re-entry that may allow tissue regeneration. Inthe present review we discuss the possibility of acontinuous genetic modulation of stem cells by a MV-mediated transfer of information between cells.