Project Details
Projekt
Modulation of human endogenous retroviruses (HERVs) by CRISPR in human pluripotent stem cells
Applicant
Dr. Michelle Vincendeau
Subject Area
Cell Biology
Virology
Virology
Term
from 2015 to 2017
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 282609876
The human genome is composed of a considerable number of endogenous retroviral elements (ERVs). ERVs are relics of ancestral infectious retroviruses, whose proviruses have invaded the germ-line long time ago. Around 500.000 endogenous long terminal repeat (LTR) sequences from retroviral origin can be found in the human genome. Many of these LTRs are still transcriptionally active and can thereby influence the expression of neighboring genes. Recent studies report that at least 6% of the human genes are controlled by human endogenous retroviral (HERV) LTRs. Therefore, HERVs are suggested as an important force in the genome evolution and adaptation of an organism to altered environmental conditions. Different studies highlight a critical role of HERVs in activating gene expression in hPSCs and thereby contributing to host cell fate decisions. However, the basic molecular mechanisms are still poorly understood. Thus, it is of particular interest to uncover the connection of HERVs and cell biological processes in human pluripotent stem cells in a more systematic fashion. This aim will be realized in this approach by applying the novel CRISPR technology. Specific HERV LTR promoters will be modulated (activated or inhibited) using CRISPR to investigate their influence on the gene signature of hPSCs and consequently on stem cell differentiation processes. This innovative approach utilizes a novel technology that for the first time provides the unique opportunity to systematically demonstrate that HERVs are not only leftovers from ancient infections in the human genome, but more importantly they are in fact active players of genome regulation.
DFG Programme
Research Fellowships
International Connection
USA
