# Unique and Conserved Endoplasmic Reticulum Stress Responses in Neuroendocrine Cells

## TL;DR

The study finds that endocrine cells share some ER stress responses but also have unique ones, which could explain differences in their vulnerability to stress.

## Contribution

The work identifies both conserved and cell-type-specific transcriptional responses to ER stress in neuroendocrine cells.

## Key findings

- All tested endocrine cell types showed responses to ER stress, including activation of core UPR genes.
- Comparative analysis revealed both shared and unique gene expression patterns across cell types.
- The data suggest novel candidate genes that may influence cell-specific responses to ER stress.

## Abstract

What are the main findings?
ER stress induces core unfolded protein response genes across neuroendocrine cell types, as well as unique transcriptional programs.Comparative transcriptomics reveals concordant and discordant responses to ER stress, highlighting potential roles of novel gene candidates.

ER stress induces core unfolded protein response genes across neuroendocrine cell types, as well as unique transcriptional programs.

Comparative transcriptomics reveals concordant and discordant responses to ER stress, highlighting potential roles of novel gene candidates.

What are the implications of the main findings?
Discordant gene expression may explain differences in susceptibility to ER stress-induced dysfunction and death.An interactive web tool enables custom end-user analysis of neuroendocrine cell ER stress responses.

Discordant gene expression may explain differences in susceptibility to ER stress-induced dysfunction and death.

An interactive web tool enables custom end-user analysis of neuroendocrine cell ER stress responses.

Endocrine cells are dedicated to the production and processing of hormones, from peptides to small molecules, to regulate key physiological processes, including glucose homeostasis and metabolism. Because of this relatively high productivity, endocrine cells must handle a variety of stresses from oxidative stress to the unfolded protein response of the endoplasmic reticulum (UPRER). While much is known about the major pathways regulating the UPRER, the roles of endocrine cell type-specific, context-dependent, and time-dependent transcriptional changes are not well explored. To identify unique and shared responses to the UPRER across a subset of endocrine cell types, we tested representative lines for β-cells (insulin), α-cells (glucagon), δ-cells (somatostatin), X/A-cells (ghrelin), L-cells (glucagon-like peptide 1 (GLP1)), and thyrotropes (thyroid hormone and thyroglobulin). We exposed each cell type to the canonical ER stressor thapsigargin for 6 and 24 h, or vehicle for 24 h, and performed mRNA sequencing. Analysis of the data showed all lines responded to thapsigargin. Comparisons of differentially expressed genes between each line revealed both shared and unique transcriptional signatures. These data represent a valuable mineable set of candidate genes that may have cell type-specific functions during the UPRER and have the potential to lead to a new understanding of how different endocrine cells mitigate or succumb to ER stress.