GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE334nnn/GSE334846/primaryOK200OtherMus musculusOtherhttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE334846GEOGSEfalseDiscovery of Tcf7 regulators with clonally-resolved CRISPR screens identifies Trim28 as a mediator of CD8 T cell differentiation in tumors [CRISPR Screen]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.2026/06/30GSE334846GSM9798390GSM9798391GSM9798392GSM9798393GSM9798398GSM9798376GSM9798410GSM9798399GSM9798377GSM9798378GSM9798411GSM9798412GSM9798379GSM9798394GSM9798395GSM9798373GSM9798396GSM9798374GSM9798375GSM9798397GSM9798417GSM9798413GSM9798414GSM9798415GSM9798416GSM9798380GSM9798381GSM9798382GSM9798387GSM9798388GSM9798389GSM9798400GSM9798401GSM9798383GSM9798384GSM9798385GSM9798386GSM9798406GSM9798407GSM9798408GSM9798409GSM9798402GSM9798403GSM9798404GSM97984051905716417334846Mus musculus