GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE334nnn/GSE334890/primary200OKTranscriptomicsMus musculus OtherExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE334890GEOGSEfalseDiscovery of Tcf7 regulators with clonally-resolved CRISPR screens identifies Trim28 as a mediator of CD8 T cell differentiation in tumorsStem-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.2026/07/09GSE334890GSM9801645GSM9801667GSM9801668GSM9801646GSM9801665GSM9801643GSM9801666GSM9801644GSM9801663GSM9801641GSM9801642GSM9801664GSM9801661GSM9801662GSM9801640GSM9801629GSM9801649GSM9801628GSM9801669GSM9801647GSM9801648GSM9801660GSM9801634GSM9801656GSM9801657GSM9801635GSM9801654GSM9801632GSM9801655GSM9801633GSM9801674GSM9801652GSM9801630GSM9801631GSM9801675GSM9801653GSM9801672GSM9801650GSM9801651GSM9801673GSM9801638GSM9801639GSM9801658GSM9801636GSM9801659GSM9801637GSM9801670GSM980167134290334890Mus musculus