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Diverging regulation of Bach2 protein and RNA expression determine cell fate in early B cell response.

ABSTRACT: During the early phase of primary humoral responses, activated B cells can differentiate into different types of effector cells, dependent on B cell receptor affinity for antigen. However, the pivotal transcription factors governing these processes remain to be elucidated. Here, we show that transcription factor Bach2 protein in activated B cells is transiently induced by affinity-related signals and mechanistic target of rapamycin complex 1 (mTORC1)-dependent translation to restrain their expansion and differentiation into plasma cells while promoting memory and germinal center (GC) B cell fates. Affinity-related signals also downregulate Bach2 mRNA expression in activated B cells and their descendant memory B cells. Sustained and higher concentrations of Bach2 antagonize the GC fate. Repression of Bach2 in memory B cells predisposes their cell-fate choices upon memory recall. Our study reveals that differential dynamics of Bach2 protein and transcripts in activated B cells control their cell-fate outcomes and imprint the fates of their descendant effector cells.

SUBMITTER: Hu Q

PROVIDER: S-EPMC9550188 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature

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Diverging regulation of Bach2 protein and RNA expression determine cell fate in early B cell response.

Hu Qianwen Q Xu Tingting T Zhang Min M Zhang Heng H Liu Yongbo Y Li Hua-Bing HB Chen Chiqi C Zheng Junke J Zhang Zhen Z Li Fubin F Shen Nan N Zhang Wenqian W Melnick Ari A Huang Chuanxin C

Cell reports 20220701 1

During the early phase of primary humoral responses, activated B cells can differentiate into different types of effector cells, dependent on B cell receptor affinity for antigen. However, the pivotal transcription factors governing these processes remain to be elucidated. Here, we show that transcription factor Bach2 protein in activated B cells is transiently induced by affinity-related signals and mechanistic target of rapamycin complex 1 (mTORC1)-dependent translation to restrain their expan ...[more]

PMID: 35793628

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Project description:BackgroundCell differentiation during development is orchestrated by precisely coordinated gene expression programs. While some regulatory mechanisms are well understood, there is a significant room to explore unresolved aspects of lineage choice and cell-fate decisions, as many events in these processes are still not fully elucidated. Given that, gene expression is influenced not only by transcriptional control but also by post-transcriptional events. Here, we described the presence of post-transcriptional regulation on gene expression during lineage commitment across all three embryonic germ layers. We employed monolayer differentiation protocols to map early transcriptional and post-transcriptional events in human embryonic stem cell specification. This approach included obtaining representative populations from the three germ layers, followed by sequencing of both polysome-bound and total RNAs.ResultsWe characterized our model by its unique expression profile and the presence of specific markers for each differentiation. RNA sequencing revealed a consistent pattern of gene upregulated and downregulated when comparing the transcriptome and translatome during the differentiation of all three germ layers. By comparing these datasets, we identified genes subjected to post-transcriptional regulation in all germ layer differentiations and categorized the nature of this regulation. GO analysis demonstrated that polysome profiling serves as a complementary technique, capturing nuances that may be overlooked when analyzing only the transcriptome. Finally, we directly compared the transcriptome and translatome to identify genes actively recruited to the translation machinery, uncovering unique features specific to each germ layer.ConclusionsSubstantial post-transcriptional modulation was found during germ layer commitment, emphasizing the translatome potency in capturing nuanced gene expression regulation. These findings highlight the post-transcriptional regulation's critical role in early embryonic development, offering new insights into the molecular mechanisms of cell differentiation.

Dataset Information

Diverging regulation of Bach2 protein and RNA expression determine cell fate in early B cell response.

Publications

Diverging regulation of Bach2 protein and RNA expression determine cell fate in early B cell response.

Similar Datasets

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