2019 Vol. 10, No. 7

This is the image for the esophagus after oncogenic Krasexpression. The cells in green show SOX2+ lineage-tracedcells in the hyperplasia. Magenta color marks proliferative cells(KI67+ cells) while blue color does nuclear.
Weisun Tao: a pioneer of biochemistry in China
Tianwei He
2019, 10(7): 467-469. doi: 10.1007/s13238-017-0383-9
Human germline editing: Insights to future clinical treatment of diseases
Yanni Li, Xiang Jin Kang, Jeremy Kah Sheng Pang, Boon Seng Soh, Yang Yu, Yong Fan
2019, 10(7): 470-475. doi: 10.1007/s13238-018-0594-8
Basic and translational aging research in China: present and future
Xiaojuan He, Moshi Song, Jing Qu, Yansu Guo, Heqi Cao, Ruijuan Sun, Guang-Hui Liu, Yong Shen, Major Program Expert Group
2019, 10(7): 476-484. doi: 10.1007/s13238-019-0617-0
The percentage of elderly people in the world is increasing at an unprecedented pace; so it is in China, which has the world's largest population and a high ratio of the seniors (aged 60 and above) to working-age adults. The growing elderly population is presenting a major social challenge. Accordingly, it is not only imperative as a national strategic demand but also promises great scientific values to understand the biological process of aging, explore the mystery of healthy aging, delay the aging process, and treat the age-related diseases. This Perspective summarizes past and present advances of the basic and translational aging research in China and offers perspectives on future endeavors in this area.
Research articles
Mutations in foregut SOX2+ cells induce efficient proliferation via CXCR2 pathway
Tomoaki Hishida, Eric Vazquez-Ferrer, Yuriko Hishida-Nozaki, Ignacio Sancho-Martinez, Yuta Takahashi, Fumiyuki Hatanaka, Jun Wu, Alejandro Ocampo, Pradeep Reddy, Min-Zu Wu, Laurie Gerken, Reuben J. Shaw, Concepcion Rodriguez Esteban, Christopher Benner, Hiroshi Nakagawa, Pedro Guillen Garcia, Estrella Nuñez Delicado, Antoni Castells, Josep M. Campistol, Guang-Hui Liu, Juan Carlos Izpisua Belmonte
2019, 10(7): 485-495. doi: 10.1007/s13238-019-0630-3
Identification of the precise molecular pathways involved in oncogene-induced transformation may help us gain a better understanding of tumor initiation and promotion. Here, we demonstrate that SOX2+ foregut epithelial cells are prone to oncogenic transformation upon mutagenic insults, such as KrasG12D and p53 deletion. GFP-based lineage-tracing experiments indicate that SOX2+ cells are the cells-of-origin of esophagus and stomach hyperplasia. Our observations indicate distinct roles for oncogenic KRAS mutation and P53 deletion. p53 homozygous deletion is required for the acquisition of an invasive potential, and KrasG12D expression, but not p53 deletion, suffices for tumor formation. Global gene expression analysis reveals secreting factors upregulated in the hyperplasia induced by oncogenic KRAS and highlights a crucial role for the CXCR2 pathway in driving hyperplasia. Collectively, the array of genetic models presented here demonstrate that stratified epithelial cells are susceptible to oncogenic insults, which may lead to a better understanding of tumor initiation and aid in the design of new cancer therapeutics.
Tongue coating microbiome as a potential biomarker for gastritis including precancerous cascade
Jiaxing Cui, Hongfei Cui, Mingran Yang, Shiyu Du, Junfeng Li, Yingxue Li, Liyang Liu, Xuegong Zhang, Shao Li
2019, 10(7): 496-509. doi: 10.1007/s13238-018-0596-6
The development of gastritis is associated with an increased risk of gastric cancer. Current invasive gastritis diagnostic methods are not suitable for monitoring progress. In this work based on 78 gastritis patients and 50 healthy individuals, we observed that the variation of tongue-coating microbiota was associated with the occurrence and development of gastritis. Twenty-one microbial species were identified for differentiating tongue-coating microbiomes of gastritis and healthy individuals. Pathways such as microbial metabolism in diverse environments, biosynthesis of antibiotics and bacterial chemotaxis were up-regulated in gastritis patients. The abundance of Campylobacter concisus was found associated with the gastric precancerous cascade. Furthermore, Campylobacter concisus could be detected in tongue coating and gastric fluid in a validation cohort containing 38 gastritis patients. These observations provided biological evidence of tongue diagnosis in traditional Chinese medicine, and indicated that tongue-coating microbiome could be a potential non-invasive biomarker, which might be suitable for long-term monitoring of gastritis.
Reciprocal regulation between lunapark and atlastin facilitates ER three-way junction formation
Xin Zhou, Yu He, Xiaofang Huang, Yuting Guo, Dong Li, Junjie Hu
2019, 10(7): 510-525. doi: 10.1007/s13238-018-0595-7
Three-way junctions are characteristic structures of the tubular endoplasmic reticulum (ER) network. Junctions are formed through atlastin (ATL)-mediated membrane fusion and stabilized by lunapark (Lnp). However, how Lnp is preferentially enriched at three-way junctions remains elusive. Here, we showed that Lnp loses its junction localization when ATLs are deleted. Reintroduction of ATL1 R77A and ATL3, which have been shown to cluster at the junctions, but not wild-type ATL1, relocates Lnp to the junctions. Mutations in the Nmyristoylation site or hydrophobic residues in the coiled coil (CC1) of Lnp N-terminus (NT) cause mis-targeting of Lnp. Conversely, deletion of the lunapark motif in the C-terminal zinc finger domain, which affects the homooligomerization of Lnp, does not alter its localization. Purified Lnp-NT attaches to the membrane in a myristoylation-dependent manner. The mutation of hydrophobic residues in CC1 does not affect membrane association, but compromises ATL interactions. In addition, Lnp-NT inhibits ATL-mediated vesicle fusion in vitro. These results suggest that CC1 in Lnp-NT contacts junction-enriched ATLs for proper localization; subsequently, further ATL activity is limited by Lnp after the junction is formed. The proposed mechanism ensures coordinated actions of ATL and Lnp in generating and maintaining three-way junctions.
Neuroendocrine characteristics of induced pluripotent stem cells from polycystic ovary syndrome women
Zheying Min, Yue Zhao, Jing Hang, Yun Ren, Tao Tan, Yong Fan, Yang Yu
2019, 10(7): 526-532. doi: 10.1007/s13238-018-0600-1
Equilibria between the K+ binding and cation vacancy conformations of potassium channels
Yao He, Bo Zhang, Hao Dong, Penglin Xu, Xiaoying Cai, Ting Zhou, Mu Yu, Jun Liang, Xiao Zheng, Changlin Tian
2019, 10(7): 533-537. doi: 10.1007/s13238-019-0609-0
HBB-deficient Macaca fascicularis monkey presents with human β-thalassemia
Yan Huang, Chenhui Ding, Puping Liang, Duanduan Li, Yu Tang, Wei Meng, Hongwei Sun, Hongyu Lu, Yu Chen, Xueying Chen, Qunshan Huang, Jianpei Fang, Canquan Zhou, Shihua Yang, Junjiu Huang
2019, 10(7): 538-542. doi: 10.1007/s13238-019-0627-y
Correction to: A binding-block ion selective mechanism revealed by a Na/K selective channel
Jie Yu, Bing Zhang, Yixiao Zhang, Cong-qiao Xu, Wei Zhuo, Jingpeng Ge, Jun Li, Ning Gao, Yang Li, Maojun Yang
2019, 10(7): 543-543. doi: 10.1007/s13238-019-0619-y