Qiu Jinjun, Zhu Peng, Shi Xing, Xia Jinquan, Dong Shaowei, Chen Liqun
Shenzhen Pingshan District People's Hospital, Pingshan Hospital, Southern Medical University, Shenzhen, China.
Clinical Laboratory, Shenzhen Pingshan District People's Hospital, Pingshan Hospital, Southern Medical University, Shenzhen, China.
Front Endocrinol (Lausanne). 2025 Jan 13;15:1532609. doi: 10.3389/fendo.2024.1532609. eCollection 2024.
Type 2 diabetes (T2D) has become a significant global health threat, yet its precise causes and mechanisms remain unclear. This study aims to identify gene expression patterns specific to T2D pancreatic islet cells and to explore the potential role of pancreatic stellate cells (PSCs) in T2D progression through regulatory networks involving lncRNA-mRNA interactions.
In this study, we screened for upregulated genes in T2D pancreatic islet samples using bulk sequencing (bulkseq) datasets and mapped these gene expression profiles onto three T2D single-cell RNA sequencing (scRNAseq) datasets. The identified T2D-specific gene features were further validated in an additional T2D scRNAseq dataset, a T1D scRNAseq dataset, and a T2D bulkseq dataset. To investigate regulatory networks, we analyzed the potential lncRNA-mRNA interactions within T2D peripheral blood mononuclear cell (PBMC) bulkseq data.
Our analysis identified a specific gene panel-COL1A2, VCAN, and SULF1-that was consistently upregulated in T2D pancreatic islet samples. Expression of this gene panel was strongly associated with the activation of pancreatic stellate cells (PSCs), suggesting a unique T2D-specific signature characterized by COL1A2/VCAN/SULF1 PSCs. This signature was exclusive to T2D and was not observed in Type 1 diabetes (T1D) samples, indicating a distinct role for activated PSCs in T2D progression. Furthermore, we identified six long non-coding RNAs (lncRNAs) that potentially interact with the COL1A2/VCAN/SULF1 PSCs. These lncRNAs were mapped to a lncRNA-mRNA network, suggesting they may modulate immune responses and potentially reshape the immune microenvironment in T2D.
Our findings highlight the potential immune-regulatory role of PSCs in T2D and suggest that PSC-related lncRNA-mRNA networks could serve as novel therapeutic targets for T2D treatment. This research provides insights into PSCs as a modulator in T2D progression, paving the way for innovative treatment strategies.
2型糖尿病（T2D）已成为全球重大的健康威胁，但其确切病因和机制仍不清楚。本研究旨在确定T2D胰岛细胞特有的基因表达模式，并通过涉及长链非编码RNA（lncRNA）-mRNA相互作用的调控网络，探索胰腺星状细胞（PSC）在T2D进展中的潜在作用。
在本研究中，我们使用批量测序（bulkseq）数据集筛选T2D胰岛样本中的上调基因，并将这些基因表达谱映射到三个T2D单细胞RNA测序（scRNAseq）数据集上。在另一个T2D scRNAseq数据集、一个1型糖尿病（T1D）scRNAseq数据集和一个T2D bulkseq数据集中进一步验证了所确定的T2D特异性基因特征。为了研究调控网络，我们分析了T2D外周血单个核细胞（PBMC）bulkseq数据中潜在的lncRNA-mRNA相互作用。
我们的分析确定了一个特定的基因组合——COL1A2、VCAN和SULF1——在T2D胰岛样本中持续上调。该基因组合的表达与胰腺星状细胞（PSC）的激活密切相关，提示以COL1A2/VCAN/SULF1 PSC为特征的独特的T2D特异性特征。这种特征是T2D特有的，在1型糖尿病（T1D）样本中未观察到，表明激活的PSC在T2D进展中具有独特作用。此外，我们确定了六个可能与COL1A2/VCAN/SULF1 PSC相互作用的长链非编码RNA（lncRNA）。这些lncRNA被映射到一个lncRNA-mRNA网络，提示它们可能调节免疫反应，并可能重塑T2D中的免疫微环境。
我们的研究结果突出了PSC在T2D中的潜在免疫调节作用，并表明PSC相关的lncRNA-mRNA网络可作为T2D治疗的新型治疗靶点。本研究为PSC作为T2D进展中的调节剂提供了见解，为创新治疗策略铺平了道路。
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