GSE159880
The DEAD-box helicase DDX56 is a conserved stemness regulator in normal and cancer stem cells
A common and shared biology across diverse animal species is that adult tissue homeostasis is ultimately regulated by stem cell proliferation, differentiation, and self-renewal. Aberrant activation of “stemness” programs is deleterious at organismal level, and commonly observed in human cancers. However, identifying key stemness genes in the milieu of thousands of genes dysregulated in a given human cancer is challenging. Here, using a comparative genomics approach between planarians and humans, we identify and functionally screen 76 highly conserved, putative stemness regulators in vivo that are also candidate drivers of stemness in human glioblastoma, a highly aggressive, stem-cell driven cancer with limited treatment options. We selected the helicase DDX56, and demonstrate a conserved role in regulating aspects of stemness across 4 normal and cancer stem cell systems: planarian adult stem cells; mouse embryonic neural stem cells; human glioma neural stem cells; and a fly model of glioblastoma. We demonstrate that DDX56 is required for self-renewal and survival of stem cells across the systems. Using planarians, we show that when DDX56 is lost, stem cells dysregulate expression of ribosomal RNAs and lose nucleolar integrity prior to stem cell death. Altogether, our study demonstrates the power of a comparative genomic approach to discover deeply conserved stemness regulators and actionable target genes relevant to human cancer. Overall design: Smed-ddx56(RNAi) animals were fed 3 times over 6 days and stem cells were collected 3 days after the last feed. Approximately 500,000 X1 cells from >100 animals were isolated at on a Becton–Dickinson FACS aria. Total RNA was purified using Trizol (Invitrogen 15596026), and poly-A-selected cDNA libraries were prepared using the TruSeq kits from Illumina. For RNA-seq, samples were sequenced to a depth of 250 million paired end 125 base pair reads, and multiplexed on an Illumina HiSeq2500. Please note that the processed data file contains data compared to wild-type X1 cells previously published in GEO accessions GSE37910 (GSM929778), GSE68581 (GSM1675833) as described in the sample data processing field.