Nature | Circular ecDNA

Paper Readig

01

Circular ecDNA promotes accessible chromatin and high oncogene expression

Sihan Wu, Kristen M. Turner, Nam Nguyen, Ramya Raviram, et al.

Nature 2019

DNA encodes information not only in its sequence, but also in its shape. The human genome is segmented into chromosomes that are made of chromatin fibres folded into dynamic, hierarchical structures. By integrating ultrastructural imaging, long-range optical mapping and computational analysis of whole-genome sequencing, the authors demonstrated the structure of circular ecDNA. Firstly, the authors found that ecDNA physical structure is circular. Then data indicate that ecDNA drives massive oncogene expression and ecDNA contains highly accessible chromatin. Pan-cancer analyses reveal that oncogenes encoded on ecDNA are among the most highly expressed genes in the transcriptome of the tumours, linking increased copy number with high transcription levels. Quantitative assessment of the chromatin state reveals that although ecDNA is packaged into chromatin with intact domain structure, it lacks higher-order compaction that is typical of chromosomes and displays significantly enhanced chromatin accessibility. Furthermore, ecDNA is shown to have a significantly greater number of ultra-long-range interactions with active chromatin, which provides insight into how the structure of circular ecDNA affects oncogene function, and connects ecDNA biology with modern cancer genomics and epigenetics.

https://doi.org/10.1038/s41586-019-1763-5

02

Landscape and Dynamics of Single Immune Cells in Hepatocellular Carcinoma

Qiming Zhang, Yao He, Nan Luo, et al.

Cell 2019

Liver cancer is the third leading cause of cancer-related mortality in the world, and hepatocellular carcinoma (HCC) accounts for approximately 90% of the incidence of all liver cancers. The authors found that two scRNA-seq platforms revealed a high-resolution dynamic immune landscape in HCC. LAMP3 + DCs, arising from cDCs, can migrate from tumors to hepatic lymph nodes. Paired ligand-receptor analyses implicate the regulation of lymphocytes by LAMP3 + DCs. Macrophage subsets in tumors show distinct states and potentials to egress to ascites. Of the macrophages in tumors that exhibited distinct transcriptional states, tumor-associated macrophages (TAMs) were associated with poor prognosis, and we established the inflammatory role of SLC40A1 and GPNMB in these cells. Further, myeloid and lymphoid cells in ascites were predominantly linked to tumor and blood

origins, respectively. Integrated single-cell RNA sequencing technologies and bioinformatics approaches reveal a high-resolution immune landscape of hepatocellular carcinoma, identifying inflammatory signatures and functional states of myeloid cells as well as predictions of complex cell-cell interactions.

https://doi.org/10.1016/j.cell.2019.10.003

END