ENAapplication/xmlftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR296/040/SRR29697640/SRR29697640_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR296/044/SRR29697644/SRR29697644_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR296/048/SRR29697648/SRR29697648_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR296/047/SRR29697647/SRR29697647_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR296/050/SRR29697650/SRR29697650_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR296/043/SRR29697643/SRR29697643_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR296/037/SRR29697637/SRR29697637_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR296/039/SRR29697639/SRR29697639_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR296/054/SRR29697654/SRR29697654_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR296/052/SRR29697652/SRR29697652_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR296/051/SRR29697651/SRR29697651_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR296/043/SRR29697643/SRR29697643_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR296/048/SRR29697648/SRR29697648_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR296/042/SRR29697642/SRR29697642_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR296/049/SRR29697649/SRR29697649_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR296/046/SRR29697646/SRR29697646_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR296/045/SRR29697645/SRR29697645_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR296/042/SRR29697642/SRR29697642_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR296/049/SRR29697649/SRR29697649_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR296/050/SRR29697650/SRR29697650_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR296/040/SRR29697640/SRR29697640_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR296/041/SRR29697641/SRR29697641_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR296/053/SRR29697653/SRR29697653_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR296/054/SRR29697654/SRR29697654_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR296/038/SRR29697638/SRR29697638_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR296/037/SRR29697637/SRR29697637_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR296/041/SRR29697641/SRR29697641_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR296/051/SRR29697651/SRR29697651_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR296/047/SRR29697647/SRR29697647_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR296/046/SRR29697646/SRR29697646_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR296/044/SRR29697644/SRR29697644_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR296/045/SRR29697645/SRR29697645_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR296/052/SRR29697652/SRR29697652_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR296/038/SRR29697638/SRR29697638_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR296/053/SRR29697653/SRR29697653_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR296/039/SRR29697639/SRR29697639_2.fastq.gzprimaryOK200GenomicsCancer Growth Regulation Lab, Korea Universityhttps://www.ebi.ac.uk/ena/browser/view/PRJNA1131440Homo sapiensxref:PubMed:40739132To better understand the complex interplay of undifferentiated cancer cells in tumor malignancy, we have focused on the crucial mechanisms that maintain the undifferentiated state of cancer stem-like cells, which drive tumor growth and therapy resistance. Here, we have identified a protein called dehydrogenase/reductase 13 (DHRS13) abundant in undifferentiated glioblastoma cells. DHRS13 is primarily located in the mitochondria and functions as a retinaldehyde reductase, converting all-trans retinaldehyde to all-trans retinol with a high affinity for NADPH. Remarkably when we deplete DHRS13 from these cells, we observe a significant decrease in tumor initiation and progression. Mechanistically, DHRS13 prevents these cells from differentiating by blocking retinoic acid signaling, thereby maintaining their undifferentiated state. Additionally, depletion of DHRS13 results in mitochondrial reactive oxygen species-driven mitophagy and cell death. These findings hold promise for the development of novel strategies to target undifferentiated cancer cells and potentially leading to improved treatment outcomes. Overall design: RNA sequencing was performed at the Beijing Genomics Institute (BGI, Shenzhen, China). Raw fragments per kilobase million (FPKM) and probability values (PA) were calculated using the performer’s algorithm and used for further analysis. Genes with PA > 0.8, whose expression levels increased or decreased by more than 2-fold after the knockdown of DHRS13, were grouped and designated as DEGs.ENAfalseThe short-chain dehydrogenases/reductase DHRS13 suppresses differentiation and mitophagy in glioma cells by modulating retinoic acid signaling and mitochondrial ROSThe short-chain dehydrogenases/reductase DHRS13 suppresses differentiation and mitophagy in glioma cells by modulating retinoic acid signaling and mitochondrial ROS2025-09-242024-08-09PRJNA1131440GSE271448960640739132