{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE334nnn/GSE334846/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Other"],"species":["Mus musculus"],"gds_type":["Other"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE334846"],"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 [CRISPR Screen]","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":"GSE334846","cross_references":{"GSM":["GSM9798390","GSM9798391","GSM9798392","GSM9798393","GSM9798398","GSM9798376","GSM9798399","GSM9798410","GSM9798377","GSM9798378","GSM9798411","GSM9798412","GSM9798379","GSM9798394","GSM9798395","GSM9798373","GSM9798396","GSM9798374","GSM9798397","GSM9798375","GSM9798417","GSM9798413","GSM9798414","GSM9798415","GSM9798416","GSM9798380","GSM9798381","GSM9798382","GSM9798387","GSM9798388","GSM9798389","GSM9798400","GSM9798401","GSM9798383","GSM9798384","GSM9798385","GSM9798386","GSM9798406","GSM9798407","GSM9798408","GSM9798409","GSM9798402","GSM9798403","GSM9798404","GSM9798405"],"GPL":["19057","16417"],"GSE":["334846"],"taxon":["Mus musculus"]}}