Paper Reading
01
Metabolic landscape of the tumor microenvironment at single cell resolution
ZhengtaoXiao,Ziwei Dai&Jason W.LocasaleNature Communications ()
The tumor microenvironment is very complexityand has received growing attention for immune therapy. The intratumoralheterogeneity of cell types have unique metabolic demands that enable specificfunction. In this paper, Zhengtao Xiao et al. developed an computational pipelinefor identifying cell type-specific metabolic programs based on single-cell RNAsequencing data and 1566 metabolic genes from KEGG. They selected two scRNA-seqdatasets for human melanoma and squamous cell carcinoma of the head neck(HNSCC) to test their computational pipeline. Cluster analysis showed that malignant cells exhibited highermetabolic plasticity which likely leads to patient-specific metabolicreprogramming of cancer cells. Then, they developed a pathway activity score toquantify the activity of a metabolic pathway. It found that malignant cellsunderwent a global up-regulation of metabolic pathway activities with the samelevel of non-metabolic pathway compared to non-malignant cell. There are highermetabolic activity and variation in single malignant cells compared to bulk RNAsequence data. Subsequently, then performed PCA and GSEA to identify majorcontributors to intratumoral metabolic heterogeneity of malignant cells. OXPHOSand TCA cycle were the top-scoring pathways for both melanoma and HNSCC. Accordingto environmental factors, it suggesting that the unexpected coupling between aerobic respiration and hypoxia-related pathways is an unique feature of singlemalignant cells in the tumor microenvironment. Finally, they used scRNA-seq to characterize the metabolicfeatures of T cell and fibroblast subpopulations. These results suggested thatsubpopulations of non-malignant cells in the tumor microenvironment hadmetabolic features that differ from their behaviors in normal tissues.
/articles/s41467-019-11738-0#Sec8
02
Subsets of ILC3−ILC1-like cells generate a diversityspectrum of innate lymphoid cells in human mucosal tissues
Marina Cella, Ramya Gamini, Cristiane Sécca … Scott A.Jelinsky and Marco Colonna et al. Nature immunity ()
Innate lymphoidcells (ILCs) are the most recently discovered part of innate immune system andpaly an important role in mediating mucosal immunity, inflammation and tissuehomeostasis. There is some controversy about whether human ILC3s can convertinto ILC1-like cells in vivo. In this paper, Marina et al. used differentanalysis methods and a humanized mouse model to demonstrate that ILC3-to-ILC1plasticity exists in vivo and is common to mucosal tissues. First, theydetected four subsets of ILCs in human inflamed tonsils flow cytometry and found twoadditional populations, in addition to ILC3 and ILC1. Then they confirmed theywere ILC3–ILC1intermediate populations by transcriptome profiling, mass spectrometry and scRNA-seqanalyses. Then they constructed a humanized mouse model to demonstrated thatILC3s acquired transcription factors and cytokines characteristic of ILC1-likecells in a tissue-dependent fashion. Further, the data showed that TGF-β and IL-23 couldrepresent the tissue factors that would coordinately regulate the expression ofAiolos, T-bet and RORγt driving the transition of ILC3s to ILC1-like cells.Besides, they also detected the ILC3–ILC1 intermediate subsets in other mucosaltissues, such as gut lamina propria.
/articles/s41590-019-0425-y
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