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Spatiotemporal dynamics of Bach2 orchestrates B cell responses and fate decision II

ABSTRACT: Spatiotemporal dynamics of Bach2 orchestrates B cell responses and fate decision II

PROVIDER: PRJNA748360 | ENA |

REPOSITORIES: ENA

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Spatiotemporal dynamics of Bach2 orchestrates B cell responses and fate decision

Project description:Spatiotemporal dynamics of Bach2 orchestrates B cell responses and fate decision

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Spatiotemporal dynamics of Bach2 orchestrates B cell responses and fate decision

Project description:The molecular circuits that direct early T-dependent B cell responses and alternative cell-fate decisions remain poorly understood. Here, we show that either B cell receptor (BCR) or CD40 signals promoted mTORC1-dependent translation of the transcription factor Bach2. Transient up-regulation of Bach2 protein restrained activated B cell expansion and differentiation into plasma cell while promoting the germinal center (GC) and memory B cell fates at the pre-GC stage. However, enforced Bach2 expression facilitated memory B cell generation versus other cell fates. Mechanistically, Bach2 limited access of AP-1 factors and formed a reciprocal repression loop with IRF4. BCR and CD40 signals also down-regulated Bach2 transcript in antigen-activated B cells, and diversified its abundance in various effector populations, predisposing Bach2 protein expression and subsequent cell-fate choices during memory recall and GC reaction. Thus signaling-induced differential dynamics of Bach2 protein and mRNA in activated B cell control their cell-fate outcomes and imprint the fate of their descendant effector cells.

2021-07-18 | GSE180277 | GEO

Spatiotemporal dynamics of Bach2 orchestrates B cell responses and fate decision II

2022-06-08 | GSE180460 | GEO

BACH2 in human plasma cell fate decision

Project description:We report here the broad transcriptomic program regulated by BACH2 transcription factor. We used a well suited in vitro model of B cell differentiation to evaluate transcriptomic program governed by BACH2 leading to Plasmocyte (PC) differentiation. In this model B cells were cultured with anti-BCR, CpG, CD40L and Interleukin-2 (IL2). This Interleukin triggers PC differentiation by directly repressing BACH2 expression. We artificially inhibit BACH2 expression by siRNA and found that this condition is sufficient to trigger PC differentiation without IL2. To understand global changes induced by enforced BACH2 downregulation we compared Chip-Sequencing data between activated B Cells and BACH2 deficient B cells (siBACH2). We found that BACH2 binds more than 3000 genes across the human genome. RNAsequencing comparing IL2 drivent committed cells and siBACH2 committed cells highlighs a large common trasncriptional program shared by both conditions and involved in B cell destiny. This study provides evidence that BACH2 is a guardian of B cell fate.

2017-08-29 | GSE102460 | GEO

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Stepwise cell fate decision pathways during osteoclastogenesis at single-cell resolution

Project description:To unveil cell fate decision pathways during osteoclast differentiation at single-cell resolution, we performed single-cell RNA sequencing (scRNA-seq) on the osteoclast culture system, in parallel with bulk RNA-seq and proteome analyses

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Project description:BACH2 in human plasma cell fate decision

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