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Characterizing control of memory CD8 T cell differentiation by BTB-ZF transcription factor Zbtb20 using single cell RNA-sequencing

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE234576 | GEO | 2023/06/30

REPOSITORIES: GEO

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Characterizing control of memory CD8 T cell differentiation by BTB-ZF transcription factor Zbtb20.

Project description:Members of the BTB-ZF transcription factor family regulate the immune system. Our laboratory identified that family member Zbtb20 contributes to the differentiation, recall responses, and metabolism of CD8 T cells. Here, we report a characterization of the transcriptional and epigenetic signatures controlled by Zbtb20 at single-cell resolution during the effector and memory phases of the CD8 T cell response. Without Zbtb20, transcriptional programs associated with memory CD8 T cell formation were up-regulated throughout the CD8 T response. A signature of open chromatin was associated with genes controlling T cell activation, consistent with the known impact on differentiation. In addition, memory CD8 T cells lacking Zbtb20 were characterized by open chromatin regions with overrepresentation of AP-1 transcription factor motifs and elevated RNA- and protein-level expressions of the corresponding AP-1 components. Finally, we describe motifs and genomic annotations from the DNA targets of Zbtb20 in CD8 T cells identified by cleavage under targets and release under nuclease (CUT&RUN). Together, these data establish the transcriptional and epigenetic networks contributing to the control of CD8 T cell responses by Zbtb20.

| S-EPMC10326419 | biostudies-literature

Characterizing control of memory CD8 T cell differentiation by BTB-ZF transcription factor Zbtb20 using single cell RNA-sequencing (scRNA-Seq)

Project description:Members of the BTB-ZF transcription factor family regulate the immune system. Our lab identified that family member Zbtb20 contributes to the differentiation, recall responses and metabolism of CD8 T cells. Here, we report a characterization of the transcriptional and epigenetic signatures controlled by Zbtb20 at single-cell resolution during the effector and memory phases of the CD8 T cell response. Without Zbtb20, transcriptional programs associated with memory CD8 T cell formation were upregulated throughout the CD8 T response. A signature of open chromatin was associated with genes controlling T cell activation, consistent with the known impact on differentiation. Additionally, memory CD8 T cells lacking Zbtb20 were characterized by open chromatin regions with overrepresentation of AP-1 transcription factor motifs and elevated RNA- and protein-level expression of the corresponding AP-1 components. Finally, we describe motifs and genomic annotations from the DNA targets of Zbtb20 in CD8 T cells identified by CUT&RUN. Together, these data establish the transcriptional and epigenetic networks contributing to the control of CD8 T cell responses by Zbtb20.

2023-07-03 | GSE234575 | GEO

Characterizing control of memory CD8 T cell differentiation by BTB-ZF transcription factor Zbtb20 using single cell RNA-sequencing (scATAC-Seq)

2023-07-03 | GSE234574 | GEO

Characterizing control of memory CD8 T cell differentiation by BTB-ZF transcription factor Zbtb20 using single cell RNA-sequencing (CUT&RUN)

2023-07-03 | GSE234573 | GEO

The BTB-ZF transcription factor Zbtb20 is driven by Irf4 to promote plasma cell differentiation and longevity.

Project description:The transcriptional network regulating antibody-secreting cell (ASC) differentiation has been extensively studied, but our current understanding is limited. The mechanisms of action of known "master" regulators are still unclear, while the participation of new factors is being revealed. Here, we identify Zbtb20, a Bcl6 homologue, as a novel regulator of late B cell development. Within the B cell lineage, Zbtb20 is specifically expressed in B1 and germinal center B cells and peaks in long-lived bone marrow (BM) ASCs. Unlike Bcl6, an inhibitor of ASC differentiation, ectopic Zbtb20 expression in primary B cells facilitates terminal B cell differentiation to ASCs. In plasma cell lines, Zbtb20 induces cell survival and blocks cell cycle progression. Immunized Zbtb20-deficient mice exhibit curtailed humoral responses and accelerated loss of antigen-specific plasma cells, specifically from the BM pool. Strikingly, Zbtb20 induction does not require Blimp1 but depends directly on Irf4, acting at a newly identified Zbtb20 promoter in ASCs. These results identify Zbtb20 as an important player in late B cell differentiation and provide new insights into this complex process.

| S-EPMC4010913 | biostudies-literature

Characterizing control of memory CD8 T cell differentiation by BTB-ZF transcription factor Zbtb20 using single cell RNA-sequencing

Project description:Characterizing control of memory CD8 T cell differentiation by BTB-ZF transcription factor Zbtb20 using single cell RNA-sequencing

| PRJNA982073 | ENA

Characterizing control of memory CD8 T cell differentiation by BTB-ZF transcription factor Zbtb20 using single cell RNA-sequencing (scRNA-Seq)

Project description:Characterizing control of memory CD8 T cell differentiation by BTB-ZF transcription factor Zbtb20 using single cell RNA-sequencing (scRNA-Seq)

| PRJNA982076 | ENA

Characterizing control of memory CD8 T cell differentiation by BTB-ZF transcription factor Zbtb20 using single cell RNA-sequencing (CUT&RUN)

Project description:Characterizing control of memory CD8 T cell differentiation by BTB-ZF transcription factor Zbtb20 using single cell RNA-sequencing (CUT&RUN)

| PRJNA982078 | ENA

Characterizing control of memory CD8 T cell differentiation by BTB-ZF transcription factor Zbtb20 using single cell RNA-sequencing (scATAC-Seq)

Project description:Characterizing control of memory CD8 T cell differentiation by BTB-ZF transcription factor Zbtb20 using single cell RNA-sequencing (scATAC-Seq)

| PRJNA982077 | ENA

Zbtb20 Restrains CD8 T Cell Immunometabolism and Restricts Memory Differentiation and Antitumor Immunity.

Project description:CD8 T cell differentiation is orchestrated by dynamic metabolic changes that direct activation, proliferation, cytotoxic function, and epigenetic changes. We report that the BTB-ZF family transcriptional repressor Zbtb20 negatively regulates CD8 T cell metabolism and memory differentiation in mice. Effector and memory CD8 T cells with conditional Zbtb20 deficiency displayed enhanced mitochondrial and glycolytic metabolism, and memory CD8 T cells had enhanced spare respiratory capacity. Furthermore, Zbtb20-deficient CD8 T cells displayed increased flexibility in the use of mitochondrial fuel sources. Phenotypic and transcriptional skewing toward the memory fate was observed during the CD8 T cell response to Listeria monocytogenes Memory cells mounted larger secondary responses and conferred better protection following tumor challenge. These data suggest that inactivation of Zbtb20 may offer an approach to enhance metabolic activity and flexibility and improve memory CD8 T cell differentiation, useful attributes for T cells used in adoptive immunotherapy.

| S-EPMC7931848 | biostudies-literature

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