Endocrine cell ER stress conservation

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 (DMSO 0.1%) for 24 h and performed mRNA sequencing. Analysis of the data showed all lines responded to thapsigargin. Comparisons of up- and down-regulated genes between each line revealed both shared and unique transcriptional signatures. These data represent a valuable mineable set of candidate genes which may have cell type-specific functions during the UPRER, and have the potential to lead to new understanding about how different endocrine cells mitigate or succumb to ER stress.内分泌细胞（endocrine cells）专门负责激素的合成与加工，涵盖肽类激素至小分子激素，以调控包括血糖稳态（glucose homeostasis）与新陈代谢在内的关键生理过程。由于这类细胞的合成活性相对较高，内分泌细胞需应对多种应激刺激，从氧化应激（oxidative stress）到内质网未折叠蛋白反应（unfolded protein response of the endoplasmic reticulum, UPRER）均在其列。尽管学界对调控UPRER的主要通路已有较为充分的研究，但内分泌细胞类型特异性、环境依赖性以及时间依赖性的转录变化所发挥的作用，仍未得到充分探索。为识别不同内分泌细胞亚群对UPRER的独特与共通应答反应，我们选取了以下代表性细胞系开展实验：分泌胰岛素的β细胞、分泌胰高血糖素的α细胞、分泌生长抑素的δ细胞、分泌饥饿素的X/A细胞、分泌胰高血糖素样肽1（glucagon-like peptide 1, GLP1）的L细胞，以及分泌甲状腺激素与甲状腺球蛋白的促甲状腺细胞。我们将各细胞系分别暴露于经典内质网应激诱导剂毒胡萝卜素（thapsigargin）中6小时与24小时，同时设置仅用0.1%二甲基亚砜（DMSO）处理的溶剂对照组，处理时长为24小时，随后对所有样本进行mRNA测序（mRNA sequencing）。数据分析结果显示，所有细胞系均对毒胡萝卜素产生了明确的应激应答。对各细胞系间上调与下调基因的比较分析，揭示了共通与独特的转录组特征。本数据集包含一批极具挖掘价值的候选基因，这些基因可能在UPRER过程中发挥细胞类型特异性的功能，有望帮助学界进一步阐明不同内分泌细胞如何缓解内质网应激或是发生应激损伤的具体机制。