The Epigenetic Regulator UTX Imposes An Effector Differentiation Trajectory in Autoimmune CD8+ T Cell Stem-like Progenitors

Recent findings suggest that long-lived CD8+ progenitors can continuously replenish CD8+ mediators in pancreatic lymph node (pLN). The mechanism controlling this conversion is still unclear. T cell specific UTX-deficiency NOD mice harbor increased frequency of islet-specific progenitors population and decreased frequency of islet-specific mediators. Thus, we analyzed pLN CD8+ T cells of UTXTCD mice and WT mice in 8- and 13-week old NOD mice by scRNAseq. We performed scRNAseq on T cells isolated from pancreatic islets of 8-week-old and 13-week-old NOD WT vs UTXTCD females to compare their transcriptome profile.

最新研究表明，长寿型CD8+祖细胞（long-lived CD8+ progenitors）可在胰腺淋巴结（pancreatic lymph node, pLN）中持续补充CD8+效应细胞。目前调控这一转化过程的分子机制仍不明确。T细胞特异性UTX缺陷（UTX^TCD）非肥胖糖尿病（non-obese diabetic, NOD）小鼠体内，胰岛特异性祖细胞群的频率升高，而胰岛特异性效应细胞的频率降低。因此，本研究通过单细胞RNA测序（single-cell RNA sequencing, scRNAseq），对8周龄和13周龄的NOD小鼠的胰腺淋巴结CD8+ T细胞进行了分析。此外，我们还从8周龄及13周龄的NOD野生型（wild type, WT）与T细胞特异性UTX缺陷雌性小鼠的胰岛中分离T细胞并开展单细胞RNA测序，以对比二者的转录组特征。