2020 Vol. 11, No. 8

African swine fever is a kind of highly contagious disease ofdomestic pigs caused by African swine fever virus (ASFV),with high mortality rates approaching 90%–100%, which posea huge threat to global food safety. Recent Cryo-EM studieson ASFV particle have greatly improved our understanding ofits five-layer architecture. However, the detailed architectureof the core shell layer remains elusive due to low resolution.In this issue, Li et al. and Fu et al. report the crystal structureof ASFV structural protein p35 and p15, respectively. Theirwork indicates that these two proteins may serve as dockingscaffolds for the recruitment of host membrane and othercomponents during the virus assembly process, and furtherstabilize the mature ASFV virion.
Professor Li-Pin. King: a famous physiologist in China
Wei Gong, Fangfang Wang, Yike Ying
2020, 11(8): 543-545. doi: 10.1007/s13238-018-00582-z
DUB-independent regulation of pVHL by OTUD6B suppresses hepatocellular carcinoma
Xiaoming Dai, Jing Liu, Wenyi Wei
2020, 11(8): 546-548. doi: 10.1007/s13238-020-00721-x
Memory T cells: strategies for optimizing tumor immunotherapy
Qingjun Liu, Zhongjie Sun, Ligong Chen
2020, 11(8): 549-564. doi: 10.1007/s13238-020-00707-9
Several studies have demonstrated that memory T cells including stem cell memory (Tscm) T cells and central memory (Tcm) T cells show superior persistence and antitumor immunity compared with effector memory T (Tem) cells and effector T (Teff) cells. Furthermore, the Tcm/Teff ratio has been reported to be a predictive biomarker of immune responses against some tumors. Thus, a system-level understanding of the mechanisms underlying the differentiation of effector and memory T cells is of increasing importance for developing immunological strategies against various tumors. This review focuses on recent advances in efficacy against tumors, the origin, formation mechanisms of memory T cells, and the role of the gut microbiota in memory T cell formation. Furthermore, we summarize strategies to generate memory T cells in (ex) vivo that, might be applicable in clinical practice.
Research articles
Single-cell transcriptomic analysis of adult mouse pituitary reveals sexual dimorphism and physiologic demand-induced cellular plasticity
Yugong Ho, Peng Hu, Michael T. Peel, Sixing Chen, Pablo G. Camara, Douglas J. Epstein, Hao Wu, Stephen A. Liebhaber
2020, 11(8): 565-583. doi: 10.1007/s13238-020-00705-x
The anterior pituitary gland drives highly conserved physiologic processes in mammalian species. These hormonally controlled processes are central to somatic growth, pubertal transformation, fertility, lactation, and metabolism. Current cellular models of mammalian anteiror pituitary, largely built on candidate gene based immuno-histochemical and mRNA analyses, suggest that each of the seven hormones synthesized by the pituitary is produced by a specific and exclusive cell lineage. However, emerging evidence suggests more complex relationship between hormone specificity and cell plasticity. Here we have applied massively parallel single-cell RNA sequencing (scRNA-seq), in conjunction with complementary imaging-based single-cell analyses of mRNAs and proteins, to systematically map both cell-type diversity and functional state heterogeneity in adult male and female mouse pituitaries at single-cell resolution and in the context of major physiologic demands. These quantitative single-cell analyses reveal sex-specific cell-type composition under normal pituitary homeostasis, identify an array of cells associated with complex complements of hormone-enrichment, and undercover non-hormone producing interstitial and supporting cell-types. Interestingly, we also identified a Pou1f1-expressing cell population that is characterized by a unique multi-hormone gene expression profile. In response to two well-defined physiologic stresses, dynamic shifts in cellular diversity and transcriptome profiles were observed for major hormone producing and the putative multi-hormone cells. These studies reveal unanticipated cellular complexity and plasticity in adult pituitary, and provide a rich resource for further validating and expanding our molecular understanding of pituitary gene expression programs and hormone production.
Dephosphorylation of cGAS by PPP6C impairs its substrate binding activity and innate antiviral response
Mi Li, Hong-Bing Shu
2020, 11(8): 584-599. doi: 10.1007/s13238-020-00729-3
The cyclic GMP-AMP (cGAMP) synthase (cGAS) plays a critical role in host defense by sensing cytosolic DNA derived from microbial pathogens or mis-located cellular DNA. Upon DNA binding, cGAS utilizes GTP and ATP as substrates to synthesize cGAMP, leading to MITA-mediated innate immune response. In this study, we identified the phosphatase PPP6C as a negative regulator of cGASmediated innate immune response. PPP6C is constitutively associated with cGAS in un-stimulated cells. DNA virus infection causes rapid disassociation of PPP6C from cGAS, resulting in phosphorylation of human cGAS S435 or mouse cGAS S420 in its catalytic pocket. Mutation of this serine residue of cGAS impairs its ability to synthesize cGAMP upon DNA virus infection. In vitro experiments indicate that S420-phosphorylated mcGAS has higher affinity to GTP and enzymatic activity. PPP6Cdeficiency promotes innate immune response to DNA virus in various cells. Our findings suggest that PPP6Cmediated dephosphorylation of a catalytic pocket serine residue of cGAS impairs its substrate binding activity and innate immune response, which provides a mechanism for keeping the DNA sensor cGAS inactive in the absence of infection to avoid autoimmune response.
Crystal structure of the African swine fever virus structural protein p35 reveals its role for core shell assembly
Guobang Li, Dan Fu, Guangshun Zhang, Dongming Zhao, Mingyu Li, Xue Geng, Dongdong Sun, Yuhui Wang, Cheng Chen, Peng Jiao, Lin Cao, Yu Guo, Zihe Rao
2020, 11(8): 600-605. doi: 10.1007/s13238-020-00730-w
Structure of African swine fever virus p15 reveals its dual role for membrane-association and DNA binding
Dan Fu, Dongming Zhao, Wei Zhang, Guangshun Zhang, Mingyu Li, Zheng Zhang, Yuhui Wang, Dongdong Sun, Peng Jiao, Cheng Chen, Yu Guo, Zihe Rao
2020, 11(8): 606-612. doi: 10.1007/s13238-020-00731-9
Broad spectrum antibiotic-degrading metallo-β-lactamases are phylogenetically diverse
Marcelo Monteiro Pedroso, David W. Waite, Okke Melse, Liam Wilson, Nataša Mitić, Ross P. McGeary, Iris Antes, Luke W. Guddat, Philip Hugenholtz, Gerhard Schenk
2020, 11(8): 613-617. doi: 10.1007/s13238-020-00736-4
Correction to: EGFR signaling augments TLR4 cell surface expression and function in macrophages via regulation of Rab5a activation
Jing Tang, Bowei Zhou, Melanie J. Scott, Linsong Chen, Dengming Lai, Erica K. Fan, Yuehua Li, Qiang Wu, Timothy R. Billiar, Mark A. Wilson, Ping Wang, Jie Fan
2020, 11(8): 618-619. doi: 10.1007/s13238-019-00679-5