The Stoffel lab aimed to shed light on the hetergenity displayed by pancreatic Beta cells during metabolic stress. They applied several high throughput sequencing methods combined with real-time imagining to characterize the stress response of B cells. One of their findings was that the transcription factor FoxM1 coordinates the acute stress response in a subset of B cells. Their findings have been published in the article "FoxM1 coordinates cell division, protein synthesis, and mitochondrial activity in a subset of ? cells during acute metabolic stress" in Cell Reports.

Highlights

• Major changes in transcriptional programs occur in degranulated B cell subpopulation
• Reduced protein synthesis and ER stress precede G2/M transition and cell division
• FoxM1 decreases ER stress, protein synthesis, and mitochondrial activity
• FoxM1 binds to the mitochondrial genome and regulates mitochondrial gene expression

Summary
Pancreatic B cells display functional and transcriptional heterogeneity in health and disease. The sequence of events leading to B cell heterogeneity during metabolic stress is poorly understood. Here, we characterize B cell responses to early metabolic stress in vivo by employing RNA sequencing (RNA-seq), assay for transposase-accessible chromatin with sequencing (ATAC-seq), single-cell RNA-seq (scRNA-seq), chromatin immunoprecipitation sequencing (ChIP-seq), and real-time imaging to decipher temporal events of chromatin remodeling and gene expression regulating the unfolded protein response (UPR), protein synthesis, mitochondrial function, and cell-cycle progression. We demonstrate that a subpopulation of B cells with active UPR, decreased protein synthesis, and insulin secretary capacities is more susceptible to proliferation after insulin depletion. Alleviation of endoplasmic reticulum (ER) stress precedes the progression of the cell cycle and mitosis and ensures appropriate insulin synthesis. Furthermore, metabolic stress rapidly activates key transcription factors including FoxM1, which impacts on proliferative and quiescent B cells by regulating protein synthesis, ER stress, and mitochondrial activity via direct repression of mitochondrial-encoded genes.

Read the Publication in Cell Reports (Open Access)

Website Stoffel Lab

Figure, highlights, summary and title from Kobiita et al. (2023) Cell Rep published under a CC BY 4.0 license.