GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE334nnn/GSE334845/primaryOK200TranscriptomicsMus musculusExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE334845GEOGSEfalseDiscovery of Tcf7 regulators with clonally-resolved CRISPR screens identifies Trim28 as a mediator of CD8 T cell differentiation in tumors [RNA-Seq]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.2026/06/30GSE334845GSM9798354GSM9798310GSM9798311GSM9798355GSM9798356GSM9798312GSM9798313GSM9798357GSM9798350GSM9798351GSM9798352GSM9798353GSM9798318GSM9798319GSM9798314GSM9798358GSM9798359GSM9798315GSM9798316GSM9798317GSM9798343GSM9798300GSM9798344GSM9798345GSM9798301GSM9798302GSM9798346GSM9798340GSM9798341GSM9798342GSM9798307GSM9798308GSM9798309GSM9798303GSM9798347GSM9798348GSM9798304GSM9798305GSM9798349GSM9798306GSM9798291GSM9798292GSM9798293GSM9798370GSM9798294GSM9798371GSM9798290GSM9798299GSM9798332GSM9798333GSM9798334GSM9798335GSM9798295GSM9798372GSM9798296GSM9798297GSM9798330GSM9798331GSM9798298GSM9798336GSM9798337GSM9798338GSM9798339GSM9798360GSM9798365GSM9798288GSM9798321GSM9798322GSM9798289GSM9798366GSM9798323GSM9798367GSM9798368GSM9798324GSM9798361GSM9798362GSM9798363GSM9798320GSM9798287GSM9798364GSM9798329GSM9798325GSM9798369GSM9798326GSM9798327GSM97983281905730172334845Mus musculus