{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE334nnn/GSE334890/"]},"type":"primary"},"statusCodeValue":200,"statusCode":"OK"}],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Mus musculus"],"gds_type":[" Other","Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE334890"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Discovery of Tcf7 regulators with clonally-resolved CRISPR screens identifies Trim28 as a mediator of CD8 T cell differentiation in tumors","description":"Stem-like TCF7+ CD8 T cells sustain anti-tumor responses and support immune checkpoint blockade. We systematically identified regulators of this cell state using genome-wide CRISPR screens in primary T cells in vitro. Using random barcodes to link clonal relationships with guide identity and transcriptional states in single cells, we inferred differentiation trajectories and differentiation rates of CD8 T cells in tumors, while mitigating confounding clonal bias. We found that Trim28-deficient T cells in tumors were enriched in the TCF7+ cell state, depleted in cycling and terminal effector states, and uniquely generating a tissue resident memory (TRM)-like state with increased chromatin accessibility at known TRM loci as well as repeat elements. Despite the increase in TCF7+ CD8 T cells, loss of Trim28 did not improve tumor control, likely because of reduced effector differentiation, highlighting the need for tuning the balance and dynamics of stem-like versus effector states for effective tumor clearance.","dates":{"publication":"2026/07/09"},"accession":"GSE334890","cross_references":{"GSM":["GSM9801645","GSM9801667","GSM9801668","GSM9801646","GSM9801665","GSM9801643","GSM9801666","GSM9801644","GSM9801663","GSM9801641","GSM9801642","GSM9801664","GSM9801661","GSM9801662","GSM9801640","GSM9801629","GSM9801649","GSM9801628","GSM9801669","GSM9801647","GSM9801648","GSM9801660","GSM9801656","GSM9801634","GSM9801635","GSM9801657","GSM9801632","GSM9801654","GSM9801655","GSM9801633","GSM9801674","GSM9801652","GSM9801630","GSM9801631","GSM9801675","GSM9801653","GSM9801672","GSM9801650","GSM9801651","GSM9801673","GSM9801638","GSM9801639","GSM9801658","GSM9801636","GSM9801659","GSM9801637","GSM9801670","GSM9801671"],"GPL":["34290"],"GSE":["334890"],"taxon":["Mus musculus"]}}