2017 Vol. 8, No. 6

Hongfu Chu: World renowned entomologist
Dayong Xue, Hongxiang Han
2017, 8(6): 395-397. doi: 10.1007/s13238-016-0339-5
Research highlight
Genome-wide in vivo screen identifies host molecule in promoting cancer metastasis
Yan Gu, Yanfang Liu, Xuetao Cao
2017, 8(6): 398-400. doi: 10.1007/s13238-017-0391-9
Structure-based assessment of diseaserelated mutations in human voltage-gated sodium channels
Weiyun Huang, Minhao Liu, S. Frank Yan, Nieng Yan
2017, 8(6): 401-438. doi: 10.1007/s13238-017-0372-z
Voltage-gated sodium (Nav) channels are essential for the rapid upstroke of action potentials and the propagation of electrical signals in nerves and muscles. Defects of Nav channels are associated with a variety of channelopathies. More than 1000 disease-related mutations have been identified in Nav channels, with Nav 1.1 and Nav 1.5 each harboring more than 400 mutations. Nav channels represent major targets for a wide array of neurotoxins and drugs. Atomic structures of Nav channels are required to understand their function and disease mechanisms. The recently determined atomic structure of the rabbit voltage-gated calcium (Cav) channel Cav 1.1 provides a template for homology-based structural modeling of the evolutionarily related Nav channels. In this Resource article, we summarized all the reported disease-related mutations in human Nav channels, generated a homologous model of human Nav 1.7, and structurally mapped disease-associated mutations. Before the determination of structures of human Nav channels, the analysis presented here serves as the base framework for mechanistic investigation of Nav channelopathies and for potential structure-based drug discovery.
The role of mitochondria in osteogenic, adipogenic and chondrogenic differentiation of mesenchymal stem cells
Qianqian Li, Zewen Gao, Ye Chen, Min-Xin Guan
2017, 8(6): 439-445. doi: 10.1007/s13238-017-0385-7
Mesenchymal stem cells (MSCs) are progenitors of connective tissues, which have emerged as important tools for tissue engineering due to their differentiation potential along various cell types. In recent years, accumulating evidence has suggested that the regulation of mitochondria dynamics and function is essential for successful differentiation of MSCs. In this paper, we review and provide an integrated view on the role of mitochondria in MSC differentiation. The mitochondria are maintained at a relatively low activity level in MSCs, and upon induction, mtDNA copy number, protein levels of respiratory enzymes, the oxygen consumption rate, mRNA levels of mitochondrial biogenesis-associated genes, and intracellular ATP content are increased. The regulated level of mitochondrial ROS is found not only to influence differentiation but also to contribute to the direction determination of differentiation. Understanding the roles of mitochondrial dynamics during MSC differentiation will facilitate the optimization of differentiation protocols by adjusting biochemical properties, such as energy production or the redox status of stem cells, and ultimately, benefit the development of new pharmacologic strategies in regenerative medicine.
Common and distinct regulation of human and mouse brown and beige adipose tissues: a promising therapeutic target for obesity
Xuejiao Liu, Christopher Cervantes, Feng Liu
2017, 8(6): 446-454. doi: 10.1007/s13238-017-0378-6
Obesity, which underlies various metabolic and cardiovascular diseases, is a growing public health challenge for which established therapies are inadequate. Given the current obesity epidemic, there is a pressing need for more novel therapeutic strategies that will help adult individuals to manage their weight. One promising therapeutic intervention for reducing obesity is to enhance energy expenditure. Investigations into human brown fat and the recently discovered beige/brite fat have galvanized intense research efforts during the past decade because of their pivotal roles in energy dissipation. In this review, we summarize the evolution of human brown adipose tissue (hBAT) research and discuss new in vivo methodologies for evaluating energy expenditure in patients. We highlight the differences between human and mouse BAT by integrating and comparing their cellular morphology, function, and gene expression profiles. Although great advances in hBAT biology have been achieved in the past decade, more cellular models are needed to acquire a better understanding of adipose-specific processes and molecular mechanisms. Thus, this review also describes the development of a human brown fat cell line, which could provide promising mechanistic insights into hBAT function, signal transduction, and development. Finally, we focus on the therapeutic potential and current limitations of hBAT as an anti-glycemic, anti-lipidemic, and weight loss-inducing ‘metabolic panacea’.
Research article
Oncogenic miR-19a and miR-19b co-regulate tumor suppressor MTUS1 to promote cell proliferation and migration in lung cancer
Yuanyuan Gu, Shuoxin Liu, Xiaodan Zhang, Guimin Chen, Hongwei Liang, Mengchao Yu, Zhicong Liao, Yong Zhou, Chen-Yu Zhang, Tao Wang, Chen Wang, Junfeng Zhang, Xi Chen
2017, 8(6): 455-466. doi: 10.1007/s13238-017-0393-7
MTUS1 (microtubule-associated tumor suppressor 1) has been identified that can function as a tumor suppressor gene in many malignant tumors. However, the function and mechanisms underlying the regulation of MTUS1 are unclear. In the present study, we reported that miR-19a and miR-19b (miR-19a/b) promote proliferation and migration of lung cancer cells by targeting MTUS1. First, MTUS1 was proved to function as a tumor suppressor in lung cancer and was linked to cell proliferation and migration promotion. Second, an inverse correlation between miR-19a/b expression and MTUS1 mRNA/protein expression was noted in human lung cancer tissues. Third, MTUS1 was appraised as a direct target of miR-19a/b by bioinformatics analysis. Fourth, direct MTUS1 regulation by miR-19a/b in lung cancer cells was experimentally affirmed by cell transfection assay and luciferase reporter assay. Finally, miR-19a/b were shown to cooperatively repress MTUS1 expression and synergistically regulate MTUS1 expression to promote lung cancer cell proliferation and migration. In conclusion, our findings have provided the first clues regarding the roles of miR-19a/b, which appear to function as oncomirs in lung cancer by downregulating MTUS1.
Copy number variants of ABCF1, IL17REL, and FCGR3A are associated with the risk of gout
Zheng Dong, Yuan Li, Jingru Zhou, Shuai Jiang, Yi Wang, Yulin Chen, Dongbao Zhao, Chengde Yang, Qiaoxia Qian, Yanyun Ma, Hongjun He, Hengdong Ji, Yajun Yang, Xiaofeng Wang, Xia Xu, Yafei Pang, Hejian Zou, Li Jin, Feng Zhang, Jiucun Wang
2017, 8(6): 467-470. doi: 10.1007/s13238-017-0401-y
Erratum to: Highly efficient generation of biallelic reporter gene knock-in mice via CRISPR-mediated genome editing of ESCs
Yanliang Wang,  Junhong Li,  Jinzhu Xiang,  Bingqiang Wen,  Haiyuan Mu, Wei Zhang, Jianyong Han
2017, 8(6): 471-472. doi: 10.1007/s13238-017-0392-8