SATB1 is a key regulator of quiescence in stem-like CD8+ T cells

ABSTRACT: Cytotoxic T-cell immunity in response to chronic infection and cancer is sustained by a self-renewing population known as the progenitor CD8+ T (TPRO) cells. These TPRO cells exhibit stem-like characteristics, including quiescence, multipotency, and self-renewal, which are the cardinal features of memory T cells. However, the mechanisms that sustain their stem-like properties under chronic antigen stimulation remain unclear. In this study, we identified SATB1 as a shared feature that is specifically enriched in both TPRO and memory CD8+ T cells. While the roles of SATB1 in stem-like CD8+ T cells remain unknown, its function as an epigenetic regulator in promoting quiescence in hematopoietic stem cells led us to hypothesize that SATB1 plays a pivotal role in regulating the stemness of TPRO and memory CD8+ T cells. To test this hypothesis, we employed CRISPR-mediated gene editing to delete the Satb1 gene specifically in CD8+ T cells. During chronic LCMV infection, we found that SATB1-deficient CD8+ T cells failed to maintain the TPRO subset and instead showed an enhanced transition toward terminally differentiated cells. Similarly, SATB1 deficiency during acute viral infection impaired the formation of memory CD8+ T cells. Mechanistically, our multi-omic assays revealed that SATB1 regulates the chromatin accessibility, transcriptional activities, and genomic architecture of stemness-associated genes, such as Tcf7, Bach2, and Myb. Overall, our results underscore the critical role of SATB1 in maintaining the transcriptional and epigenetic features of stem-like CD8+ T cells, shedding light on the previously unappreciated regulatory mechanisms that sustain the stemness of antigen-specific CD8+ T cells.

ORGANISM(S): Mus musculus

PROVIDER: GSE302478 | GEO | 2025/07/20

REPOSITORIES: GEO