{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE334nnn/GSE334845/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Mus musculus"],"gds_type":["Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE334845"],"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 [RNA-Seq]","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":"2026/06/30"},"accession":"GSE334845","cross_references":{"GSM":["GSM9798354","GSM9798310","GSM9798311","GSM9798355","GSM9798356","GSM9798312","GSM9798313","GSM9798357","GSM9798350","GSM9798351","GSM9798352","GSM9798353","GSM9798318","GSM9798319","GSM9798314","GSM9798358","GSM9798359","GSM9798315","GSM9798316","GSM9798317","GSM9798343","GSM9798300","GSM9798344","GSM9798345","GSM9798301","GSM9798302","GSM9798346","GSM9798340","GSM9798341","GSM9798342","GSM9798307","GSM9798308","GSM9798309","GSM9798303","GSM9798347","GSM9798348","GSM9798304","GSM9798305","GSM9798349","GSM9798306","GSM9798291","GSM9798292","GSM9798293","GSM9798370","GSM9798294","GSM9798371","GSM9798290","GSM9798299","GSM9798332","GSM9798333","GSM9798334","GSM9798335","GSM9798295","GSM9798372","GSM9798296","GSM9798297","GSM9798330","GSM9798331","GSM9798298","GSM9798336","GSM9798337","GSM9798338","GSM9798339","GSM9798360","GSM9798365","GSM9798288","GSM9798321","GSM9798322","GSM9798289","GSM9798366","GSM9798323","GSM9798367","GSM9798368","GSM9798324","GSM9798361","GSM9798362","GSM9798363","GSM9798320","GSM9798287","GSM9798364","GSM9798329","GSM9798325","GSM9798369","GSM9798326","GSM9798327","GSM9798328"],"GPL":["19057","30172"],"GSE":["334845"],"taxon":["Mus musculus"]}}