Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

The transcription factors TCF1 and LEF1 promote B-1a cell homeostasis and regulatory function

ABSTRACT: B-1 cells are innate-like immune cells found abundantly in serosal cavities and their secreted antibodies are enriched for bacterial recognition1–5. The subset known as “B-1a” repress inflammation by production of regulatory molecules including IL-10 6–8. Unlike conventional B cells, which are produced daily in the bone marrow, B-1a cells are primarily generated from foetal precursors and maintained through self-renewal 9. The mechanisms regulating B-1a homeostasis and function are incompletely understood. Here we demonstrate that serosal cavity mouse and human B-1 cells as well as chronic lymphocytic leukaemia (CLL) B cells express the transcription factors TCF1 and LEF1, and circulating TCF1+LEF1+ B-1 cells increase significantly in patients with bacterial pleural infection. LEF1 is expressed from foetal B-1 progenitors, while TCF1 expression is higher in peripheral B-1a cells. TCF1 and LEF1 deficiency significantly reduces B-1a cells in mice. These transcription factors support B-1a turn-over regulating Myc targets and metabolic pathways. Upon B-1 cell activation, TCF1/LEF1 induce formation of a stem-like population, partly through IL-10 production. TCF/LEF1-deficient B-1 cells proliferate excessively, acquire an exhausted/senescent phenotype, express reduced IL-10 and PD-L1, and fail to suppress brain inflammation. These findings reveal a transcriptional program that links stemness and regulatory potential in B-1a cells.

ORGANISM(S): Mus musculus

PROVIDER: GSE294717 | GEO | 2025/08/14

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

The transcription factors TCF1 and LEF1 promote B-1a cell homeostasis and regulatory function.

Project description:B-1 cells are innate-like immune cells found abundantly in serosal cavities and their secreted antibodies are enriched for bacterial recognition1–5. The subset known as “B-1a” repress inflammation by production of regulatory molecules including IL-10 6–8. Unlike conventional B cells, which are produced daily in the bone marrow, B-1a cells are primarily generated from foetal precursors and maintained through self-renewal 9. The mechanisms regulating B-1a homeostasis and function are incompletely understood. Here we demonstrate that serosal cavity mouse and human B-1 cells as well as chronic lymphocytic leukaemia (CLL) B cells express the transcription factors TCF1 and LEF1, and circulating TCF1+LEF1+ B-1 cells increase significantly in patients with bacterial pleural infection. LEF1 is expressed from foetal B-1 progenitors, while TCF1 expression is higher in peripheral B-1a cells. TCF1 and LEF1 deficiency significantly reduces B-1a cells in mice. These transcription factors support B-1a turn-over regulating Myc targets and metabolic pathways. Upon B-1 cell activation, TCF1/LEF1 induce formation of a stem-like population, partly through IL-10 production. TCF/LEF1-deficient B-1 cells proliferate excessively, acquire an exhausted/senescent phenotype, express reduced IL-10 and PD-L1, and fail to suppress brain inflammation. These findings reveal a transcriptional program that links stemness and regulatory potential in B-1a cells.

2025-08-14 | GSE290505 | GEO

The transcription factors TCF1 and LEF1 promote B-1a cell homeostasis and regulatory function.

Project description:B cells are innate-like immune cells found abundantly in serosal cavities and their secreted antibodies are enriched for bacterial recognition1–5. The subset known as “B-1a” repress inflammation by production of regulatory molecules including IL-10 6–8. Unlike conventional B cells, which are produced daily in the bone marrow, B-1a cells are primarily generated from foetal precursors and maintained through self-renewal 9. The mechanisms regulating B-1a homeostasis and function are incompletely understood. Here we demonstrate that serosal cavity mouse and human B-1 cells as well as chronic lymphocytic leukaemia (CLL) B cells express the transcription factors TCF1 and LEF1, and circulating TCF1+LEF1+ B-1 cells increase significantly in patients with bacterial pleural infection. LEF1 is expressed from foetal B-1 progenitors, while TCF1 expression is higher in peripheral B-1a cells. TCF1 and LEF1 deficiency significantly reduces B-1a cells in mice. These transcription factors support B-1a turn-over regulating Myc targets and metabolic pathways. Upon B-1 cell activation, TCF1/LEF1 induce formation of a stem-like population, partly through IL-10 production. TCF/LEF1-deficient B-1 cells proliferate excessively, acquire an exhausted/senescent phenotype, express reduced IL-10 and PD-L1, and fail to suppress brain inflammation. These findings reveal a transcriptional program that links stemness and regulatory potential in B-1a cells.

2025-08-14 | GSE298030 | GEO

Tcf1 and Lef1 regulate follicular helper T cell function eliciated by vaccination [ATAC-Seq]

Project description:The goal of this study is to determine the impact of Tcf1 and Lef1 deficiency on T follicular helper (Tfh) cells elicited by protein immunization. We demonstrate that although phenotypic Tcf1/Lef1-deficient Tfh cells were able to develop in response to vaccination, they are functionally impaired. Mechanisc studies reveal the direct regulatory effect by Tcf1 and Lef1 on transcriptome and chromatin accessibility in vaccine-elicited Tfh cells. Analysis of chromatin accessibility in WT and Tcf1/Lef1-deficient Tfh cells eliciated by vaccination.

2020-10-19 | GSE146421 | GEO

Impact of Tcf1 and Lef1 deficiency on histone marks and Tcf1 binding in CD8 T cells

Project description:Comparison of epigenome and Tcf1 occupancy between control and Tcf1/Lef1-deficient CD8 T cells Control mice or those are deficient for Tcf1 and Lef1 transcription factors (deleted by CD4-Cre) were used to isolate thymocytes. The thymocytes were surface-stained to identify TCRbeta high, CD69â, CD24â CD8+ subsets. These cells were sorted for ChIPseq analysis of various histone marks. Control mice or those are deficient for Tcf1 (deleted by CD4-Cre) were used to isolate thymocytes. The splenocytes were surface-stained to identify TCRbeta high, CD8+ subsets. These cells were sorted for ChIPseq analysis of Tcf1 binding locations.

2016-02-12 | E-GEOD-73239 | biostudies-arrayexpress

The transcriptome analysis of Treg subset

Project description:The transcriptome analysis of WT and Tcf7/Lef1 double knockout (dKO) Treg subset CD4+ Foxp3+ T regulatory (Treg) cells are key players in preventing lethal autoimmunity and deleterious tissue inflammation. To fulfill these roles, Treg cells undergo activation and differentiate processes to acquire diverse functional properties. However, how Treg’s functional specifications are regulated during their differentiation remains poorly understood. Here we show that two TCF/LEF family transcription factors (TFs), TCF1 and LEF1 act redundantly as checkpoint regulators in peripheral Treg homeostatic differentiation and functional subset specification. We find that gradient expression of TCF1 and LEF1 distinguishes Treg cells into three distinct subsets. Sustained expression of TCF1/LEF1 retains Treg at their resting stage. Conversely, conditional knockout of TCF1 and LEF1 promotes the effector-like phenotype in bulk Treg cells, but surprisingly renders the mice susceptible to early onset of systemic autoimmunity. This uncoupling between Treg effector phenotype and their function in suppressing autoimmunity is attributed by two TCF1/LEF1-centered mechanisms. First, the ablation of TCF1 and LEF1 in Treg cells abolishes the generation of T follicular regulatory (Tfr) cells, leading to unrestrained T follicular helper (Tfh) and germinal center B cell responses. Second, TCF1 and LEF1 are required for Treg survival under competitive conditions. Thus, TCF1 and LEF1 play critical roles in Treg homeostatic maintenance and Tfr generation.

2019-09-05 | GSE117726 | GEO

Impact of Tcf1 and Lef1 deficiency on mature CD8 thymocytes

Project description:Comparison of transcriptome between control and Tcf1/Lef1-deficient mature CD8 thymocytes Control mice or those are deficient for Tcf1 and Lef1 transcription factors (deleted by CD4-Cre) were used to isolate thymocytes. The thymocytes were surface-stained to identify TCRbeta high, CD69â, CD24â CD8+ subsets. These cells were sorted for RNAseq analysis.

2016-02-12 | E-GEOD-73238 | biostudies-arrayexpress

Tcf1 and Lef1 regulate follicular helper T cell function eliciated by vaccination [RNA-Seq]

2020-10-19 | GSE146425 | GEO