Profiling Cell Responses Under Inflammation and ER Stress Throughout β-Cell Development Across Healthy and Type 1 Diabetic Donors

Document Type

Article

Publication Date

2026

JAX Location

NYSCF

Abstract

Type 1 diabetes (T1D) is an autoimmune disease in which insulin producing β-cells of the pancreas are attacked by the immune system. This process involves a genetic predisposition in combination with environmental factors that trigger the disease specifically targeting β-cells although the etiology is not fully understood. To model this disease, induced pluripotent stem cells (iPSCs) can be used to create an infinite source of pancreatic β-cells for testing. In this study, iPSCs were differentiated into β-cells across a seven-stage process where they transitioned from 2D cultures (stages 0-4) into 3D organoids (stages 5-7). To characterize stress and inflammatory responses through β-cell development , cells from stages 0, 4, 6, and 7 of β-cell differentiation were treated with brefeldin A (BFA) to induce endoplasmic reticulum (ER) stress or proinflammatory cytokines. Quantitative PCR (qPCR) assay was successfully established complementing flow cytometry analysis to test the expression of key ER stress (BiP, ATF4, CHOP) and inflammatory genes (STAT1, CXCL10, PDL1, FAS, B2M, TNF) across the tested stages. From ER stress, a decrease in BiP and CHOP expression from stage 0 was observed alongside an increase in ATF4 across development. From cytokine exposure, an increase in STAT1, CXCL10, PDL1, FAS, and B2M was observed across the stages. In addition, we found no noticeable difference between the healthy and T1D lines but due to sample size, future testing should be performed with larger cohorts as the current data is insufficient to conclude any difference in responses between these two populations. Furthermore, while technical issues caused this differentiation to be suboptimal, a more efficient differentiation should be done to confirm the results presented here.

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