Targeting RNA helicase DDX3 in stem cell maintenance and teratoma formation.

Candace L Kerr,Venu Raman,Guus M Bol,Farhad Vesuna

doi:10.18632/genesandcancer.187

Candace L Kerr, Venu Raman + Show 2 more

Open Access

https://doi.org/10.18632/genesandcancer.187

Copy DOI

Abstract

DDX3 is an RNA helicase that has antiapoptotic properties, and promotes proliferation and transformation. Besides the role of DDX3 in transformed cells, there is evidence to indicate that DDX3 expression is at its highest levels during early embryonic development and is also expressed in germ cells of adults. Even though there is a distinct pattern of DDX3 expression during embryonic development and in adults, very little is known regarding its role in embryonic stem cells and pluripotency. In this work, we examined the relationship between DDX3 and human embryonic stem cells and its differentiated lineages. DDX3 expression was analyzed by immunohistochemistry in human embryonic stem cells and embryonal carcinoma cells. From the data obtained, it was evident that DDX3 was overexpressed in undifferentiated stem cells compared to differentiated cells. Moreover, when DDX3 expression was abrogated in multiple stem cells, proliferation was decreased, but differentiation was facilitated. Importantly, this resulted in reduced potency to induce teratoma formation. Taken together, these findings indicate a distinct role for DDX3 in stem cell maintenance.

Highlights

Despite the enormous potential of pluripotent stem cells for the treatment of human disease, a significant gap exists with respect to our understanding of the biological controls that regulate their differentiation and pluripotent nature
DEAD-Box Helicase 3 (DDX3) expression decreases with differentiation in human embryonic stem www.Genes&Cancer.com cells (ESCs) and embryonal carcinoma cells (ECCs)
Following gene expression analysis of pluripotent ESCs and unipotent progenitors of embryonic germ cells (EGCs) and ECCs known as primordial germ cells (PGCs), DDX3 was identified as one of a few genes that showed differential expression between these two cell types

Summary

Introduction

Despite the enormous potential of pluripotent stem cells for the treatment of human disease, a significant gap exists with respect to our understanding of the biological controls that regulate their differentiation and pluripotent nature. The discovery of factors that regulate stem cell maintenance began with the characterization of transcription factors that were required for stem cell self-renewal and pluripotency These factors include Oct ( known as POU5F1 (POU domain, class 5, transcription factor 1), SRY (sex determining region Y)-box 2 (Sox2), and Nanog as well as others, which are master regulators of stem cell fate [1,2,3,4]. Since their discoveries it has been realized that mechanisms must be in place for a stem cell to maintain its pluripotent state. These mechanisms have included key players in epigenetic regulation, cell cycle, and autophagy [5,6,7,8,9,10,11,12]

Methods

Results

Conclusion