Induction of recurrent break cluster genes in neural progenitor cells differentiated from embryonic stem cells in culture

• DOI: 10.1073/pnas.1922299117
• Publication Date: 2020-04-25T00:10:21Z
• Authors: Aseda Tena; Yuxiang Zhang; Nia Kyritsis; Anne Devorak; Jeffrey Zurita; Pei-Chi Wei; Frederick W. Alt
• Keywords: Progenitor

Mild replication stress enhances appearance of dozens robust recurrent genomic break clusters, termed RDCs, in cultured primary mouse neural stem and progenitor cells (NSPCs). Robust RDCs occur within genes (“RDC-genes”) that are long have roles cell communications and/or been implicated neuropsychiatric diseases or cancer. We sought to develop an vitro approach determine whether specific RDC formation is associated with development. For this purpose, we adapted a system induce (NPC) development from embryonic (ESC) lines deficient for XRCC4 plus p53, genotype DNA double-strand (DSB) persistence enhance detection. tested by our genome-wide DSB identification captures DSBs via their ability join Cas9/single-guide RNA–generated bait DSBs. In XRCC4/p53-deficient ESCs, detected seven all which were two robust. contrast, NPCs derived these ESC 29 large fraction long, transcribed also RDC-genes NSPCs. These studies suggest many present NSPCs developmentally influenced type indicate induced ESCs provides rapidly elucidate mechanistic aspects NPC formation.