文献学习062--[sc]单细胞测序解析BNT162B2诱导的心
1. Time series analysis of single-cell RNA sequencing data of PBMCs of a patient with BNT162b2-MyoC
作者对BNT162b2 (辉瑞的新冠疫苗) 诱导的心肌炎早期、eraly recovery和late recovery三个时间点的外周血进行了单细胞测序。整合注释得到22个细胞群。（细胞注释用的是scCATCH加手动注释）
2. Overall transcriptomic profiles of classical monocytes in BNT162b2-MyoC stage
Fig 2a：细胞比例结果显示三种单核细胞(c01-c03)showed the greatest increase in terms of cell number at the time of myocarditis compared to cell numbers in the late recovery state（在早期多，恢复少）
Fig 2b：DEGs的数目显示经典单核是最多的。(BTN162B2-MyoC vs early recovery)
Fig 2c：经典单核DEG的展示 (BTN162B2-MyoC vs the others)
Fig 2d：经典单核差异基因的富集通路。和早/期恢复期相比，发病期脂肪代谢通路都显著上调。
3. JUN, FOS are significantly down- regulated in classical monocytes in BNT162b2-MyoC stage
Fig 3a：为了进一步探究BNT162b2-MyoC患者的单核细胞的特性，作者将其与新冠患者PBMC（GSE150728，包括7个新冠患者和6个正常对照）、6例注射了新冠疫苗但是没有出现心肌炎的PBMC (GSE171964)、Kawasaki或新冠引起的心肌炎患者的PBMC (GSE167029，包括9个正常对照，6个新冠引起的心肌炎和2个Kawasaki) 进行了整合分析。
Fig 3b：和两个recovery时期相比，BNT162b2-MyoC的经典单核的AP-1出现显著要低。
AP-1 is a TF complex consisting of JUN, JUNB, JUND, FOS, and FOSB. The AP-1 complex is known to affect various cellular processes, such as proliferation, differentiation, apoptosis, and immune cell activation, and macrophage differentiation.
Fig 3c：scenic的结果和前面一致
Fig 3d：JUN和FOS参与调控的基因在BNT162b2-MyoC的经典单核也更低。
Fig 3e：Ultimately JUN/JUND was one of the regulons that showed the greatest up-regulation at the time of early recovery
4. Fatty acid metabolism is highly up-regulated in classical monocytes in BNT162b2-MyoC stage
Fig 4a：BNT162b2-MyoC和其他组相比的差异基因做的功能富集，发现氧化磷酸化、脂肪酸代谢和糖酵解在BNT162b2-MyoC的经典单核中显著富集。
Fig 4b：脂肪酸代谢相关基因在BNT162b2-MyoC中显著要高。
Fig 4c：gsea也是一样的结果
5. CEBPB is the major transcription factor to mediate fatty acid metabolism in classical monocytes in BNT162b2-MyoC stage
To predict the transcription factors associated with the changes in fatty acid metabolism-related genes, we explored the changes in regulon activities in classical monocytes at BNT162b2- MyoC stage.
Fig 5a：SCENIC分析的结果显示，在BNT162b2-MyoC中出现活性增加的regulon包扩CEBPB, UQCRB, CEBPD和SAP30。
Fig 5b：To explore regulon activity of the acute myocarditis phase, the regulon activity of BNT162b2-MyoC stage was compared only with early recovery stage. The regulon activity of CEBPB and CEBPD was the highest.
Fig 5c：BNT162b2-MyoC的the most enriched Motif
Fig 5d：iRegulon预测的CEBPB的靶基因包括CPT1A, ACSL1, PDK4。
Fig 5e：BNT162b2-MyoC的CEBPB 和 CEBPD的活性随着恢复逐渐降低。
Given that recent studies have highlighted the importance of fatty acid oxidation in immune activity of monocytes, especially during differentiation into macrophages, our study is meaningful in that it addressed the increased fatty acid metabolism in classical monocytes during BNT162b2-MyoC stage. Also, we suggest the possibility that CEBPB may play a critical role in this metabolic shift.
6. Classical monocytes-mediated IL-16 and CXCL signals were enhanced during BNT162B2-MyoC stage
免疫细胞的代谢变化可以通过影响细胞交互（如IL1b, IL4, IL18 和 CXCL-1等细胞因子的释放）起到重要的免疫调节作用。在前面的研究中，作者发现BNT162b2-MyoC的脂肪酸代谢增加，因此作者随后查看了经典单核和其他细胞的互作。发现IL-6和CXCL的通路显著上调。
7. Classical Monocytes receives Cytotoxic T cell-mediated incoming signals in BNT162b2-myocarditis stage
作为信号接收细胞来看，经典单核细胞主要接收Cytotoxic T的调控
