SATB1 is a key regulator of quiescence in stem-like CD8+ T cells
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PROVIDER: PRJNA1291061 | ENA |
REPOSITORIES: ENA
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Project description: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.
2025-07-20 | GSE302478 | GEO
Project description:Chronic infections and cancers induce CD8+ T cell exhaustion, but within this exhausted CD8+ T cell pool, a self-renewing, stem-like subset known as progenitor CD8+ T (TPRO) cells play a crucial role in maintaining long-term immunity. 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 preserve their stem-like properties under chronic antigen stimulation remain unclear. In this study, we identified that SATB1 as a shared feature is highly expressed in both TPRO and memory CD8+ T cells. While the role of SATB1 in stem-like CD8+ T cells remains unknown, its function as 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 Satb1 gene specifically in CD8+ T cells. Upon chronic LCMV infection, we found that SATB1-deficient CD8+ T cells failed to maintain TPRO subset with enhanced transition towards terminally differentiated cells. Similarly, the SATB1 deficiency in acute viral infection impaired the formation of memory CD8+ T cells. Mechanistically, our multi-omic assays revealed that SATB1 regulates the chromatin accessibility and transcriptional activities of stemness-associated genes, such asTcf7, Bach2,andMyb. 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.
2025-07-16 | GSE276087 | GEO
Project description:Chronic infections and cancers induce CD8+ T cell exhaustion, but within this exhausted CD8+ T cell pool, a self-renewing, stem-like subset known as progenitor CD8+ T (TPRO) cells play a crucial role in maintaining long-term immunity. 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 preserve their stem-like properties under chronic antigen stimulation remain unclear. In this study, we identified that SATB1 as a shared feature is highly expressed in both TPRO and memory CD8+ T cells. While the role of SATB1 in stem-like CD8+ T cells remains unknown, its function as 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 Satb1 gene specifically in CD8+ T cells. Upon chronic LCMV infection, we found that SATB1-deficient CD8+ T cells failed to maintain TPRO subset with enhanced transition towards terminally differentiated cells. Similarly, the SATB1 deficiency in acute viral infection impaired the formation of memory CD8+ T cells. Mechanistically, our multi-omic assays revealed that SATB1 regulates the chromatin accessibility and transcriptional activities of stemness-associated genes, such asTcf7, Bach2,andMyb. 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.
2025-07-16 | GSE275974 | GEO
Project description:Chronic infections and cancers induce CD8+ T cell exhaustion, but within this exhausted CD8+ T cell pool, a self-renewing, stem-like subset known as progenitor CD8+ T (TPRO) cells play a crucial role in maintaining long-term immunity. 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 preserve their stem-like properties under chronic antigen stimulation remain unclear. In this study, we identified that SATB1 as a shared feature is highly expressed in both TPRO and memory CD8+ T cells. While the role of SATB1 in stem-like CD8+ T cells remains unknown, its function as 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 Satb1 gene specifically in CD8+ T cells. Upon chronic LCMV infection, we found that SATB1-deficient CD8+ T cells failed to maintain TPRO subset with enhanced transition towards terminally differentiated cells. Similarly, the SATB1 deficiency in acute viral infection impaired the formation of memory CD8+ T cells. Mechanistically, our multi-omic assays revealed that SATB1 regulates the chromatin accessibility and transcriptional activities of stemness-associated genes, such asTcf7, Bach2,andMyb. 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.
2025-07-16 | GSE275969 | GEO
Project description:SATB1 is a key regulator of quiescence in stem-like CD8+ T cells [Multiome]
| PRJNA1154666 | ENA
Project description:SATB1 is a key regulator of quiescence in stem-like CD8+ T cells [ATAC-seq]
| PRJNA1153986 | ENA
Project description:SATB1 is a key regulator of quiescence in stem-like CD8+ T cells [RNA-seq]
| PRJNA1154003 | ENA
Project description:How hematopoietic stem cells (HSCs) produce specific lineages is not well understood. We searched for key factors that direct HSC to lymphopoiesis. Comparing gene expression profiles for HSCs and early lymphoid progenitors revealed that Satb1, a global chromatin regulator, was significantly induced with lymphoid lineage specification. HSCs from Satb1-null mouse were defective in lymphopoietic activity in culture, and failed to reconstitute T-lymphopoiesis in wild-type recipients. Furthermore, Satb1-transduction in HSCs, as well as in embryonic stem cells, robustly promoted their differentiation toward lymphocytes in culture. We prepared RNA samples from control or Satb1-transfected Lin- c-kitHi Sca-1+ Flt3- cells derived from WT mouse bone marrow.
2013-04-01 | E-GEOD-45566 | biostudies-arrayexpress
Project description:CD4+ and CD8+ double-positive (DP) thymocytes are at a critical stage during the T cell development in thymus. DP cells rearrange the T cell receptor gene Tcra to generate T cell receptors with TCR. Then DP cells differentiate into CD4 or CD8 single-positive (SP) thymocytes, Regulatory T cells, or invariant nature kill T cells (iNKT) according to the TCR signal. Chromatin organizer SATB1 is highly expressed in DP cells and plays an essential role in regulating Tcra rearrangement and differentiation of DP cells. Here we explored the mechanism of SATB1 orchestrating gene expression in DP cells. Single-cell RNA sequencing assay of SATB1-deficient thymocytes showed that the cell identity of DP thymocytes was changed, and the genes specifically highly expressed in DP cells were down-regulated. ChIP-seq and ATAC-seq data showed the similar tendency. The super-enhancers regulate the expressions of the DP-specific genes, and the SATB1 deficiency reduced the super-enhancer activity. Hi-C data showed that interactions in super-enhancers and between super-enhancers and promoters decreased in SATB1 deficient thymocytes. We further explored the regulation mechanism of two SATB1-regulating genes, ETS2 and Bcl6, in DP cells and found that the knockout of the super-enhancers of these two genes impaired the development of DP cells. Our research reveals that SATB1 globally regulates super-enhancers of DP cells and promotes the establishment of DP cell identity, which helps understand the role of SATB1 in thymocyte development.
2021-09-02 | GSE182995 | GEO