{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE301nnn/GSE301111/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":[" Mus musculus","Homo sapiens"],"gds_type":["Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE301111"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Dissecting cellular state alterations critical for the synergistic response and therapy resistance of the combined Abemaciclib, Temozolomide, and Radiation in DIPG PDOX models","description":"Diffuse intrinsic pontine glioma (DIPG) is a lethal pediatric brain cancer. Here, we demonstrated that combining the CDK4/6 inhibitor abemaciclib with temozolomide and radiation (the triple therapy) yields synergistic anti-tumor effects in DIPG organoids and significantly extends survival times in patient-derived orthotopic (intra-brain stem) xenograft (PDOX) models. Mechanistically, we performed scRNA-seq and identified dynamic reprogramming of tumor cell states, including the expansion of NPC-like, depletion of OPC- and AC-like subpopulations, and persistence of MES-like and mitotic-like cells, that contributed to therapeutic resistance. Pseudotime trajectory analysis further revealed therapy-induced cell fate transitions within NPC- and OPC-like compartments, including the enrichment of stem-like cells. More importantly, we discovered that an alternative trajectory—exit from stemness toward more differentiated states—may also contribute to therapeutic failure. Additionally, we identified a novel radiation-resistant subpopulation and found a new set of transcriptional targets indicative of therapeutic vulnerability. This study demonstrated the triple therapy as a promising DIPG regimen that can be rapidly translated into clinical trials and nominated new cellular and molecular targets to overcome residual disease.","dates":{"publication":"2026/08/07"},"accession":"GSE301111","cross_references":{"GSM":["GSM9075552","GSM9075553","GSM9075542","GSM9075543","GSM9075554","GSM9075544","GSM9075555","GSM9075550","GSM9075551","GSM9075549","GSM9075545","GSM9075546","GSM9075547","GSM9075548"],"GPL":["34284","34290"],"GSE":["301111"],"taxon":[" Mus musculus","Homo sapiens"],"PMID":["[42532370]"]}}