2015 Vol. 6, No. 8

News and views
To be EndMT or not to be, that is the question in pulmonary hypertension
Jianhua Xiong
2015, 6(8): 547-550. doi: 10.1007/s13238-015-0183-z
Science: a world without borders
Joel Haywood
2015, 6(8): 551-552. doi: 10.1007/s13238-015-0189-6
The roles of Mesp family proteins: functional diversity and redundancy in differentiation of pluripotent stem cells and mammalian mesodermal development
Qianqian Liang, Chen Xu, Xinyun Chen, Xiuya Li, Chao Lu, Ping Zhou, Lianhua Yin, Ruizhe Qian, Sifeng Chen, Zhendong Ling, Ning Sun
2015, 6(8): 553-561. doi: 10.1007/s13238-015-0176-y
Mesp family proteins comprise two members named mesodermal posterior 1 (Mesp1) and mesodermal posterior 2 (Mesp2). Both Mesp1 and Mesp2 are transcription factors and they share an almost identical basic helix-loop-helix motif. They have been shown to play critical regulating roles in mammalian heart and somite development. Mesp1 sits in the core of the complicated regulatory network for generation of cardiovascular progenitors while Mesp2 is central for somitogenesis. Here we summarize the similarities and differences in their molecular functions during mammalian early mesodermal development and discuss possible future research directions for further study of the functions of Mesp1 and Mesp2. A comprehensive knowledge of molecular functions of Mesp family proteins will eventually help us better understand mammalian heart development and somitogenesis as well as improve the production of specific cell types from pluripotent stem cells for future regenerative therapies.
In vitro culture of isolated primary hepatocytes and stem cell-derived hepatocyte-like cells for liver regeneration
Chenxia Hu, Lanjuan Li
2015, 6(8): 562-574. doi: 10.1007/s13238-015-0180-2
Various liver diseases result in terminal hepatic failure, and liver transplantation, cell transplantation and artificial liver support systems are emerging as effective therapies for severe hepatic disease. However, all of these treatments are limited by organ or cell resources, so developing a sufficient number of functional hepatocytes for liver regeneration is a priority. Liver regeneration is a complex process regulated by growth factors (GFs), cytokines, transcription factors (TFs), hormones, oxidative stress products, metabolic networks, and microRNA. It is well-known that the function of isolated primary hepatocytes is hard to maintain; when cultured in vitro, these cells readily undergo dedifferentiation, causing them to lose hepatocyte function. For this reason, most studies focus on inducing stem cells, such as embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), hepatic progenitor cells (HPCs), and mesenchymal stem cells (MSCs), to differentiate into hepatocyte-like cells (HLCs) in vitro. In this review, we mainly focus on the nature of the liver regeneration process and discuss how to maintain andenhance in vitrohepatic functionof isolated primary hepatocytes or stem cell-derived HLCs for liver regeneration. In this way, hepatocytes or HLCs may be applied for clinical use for the treatment of terminal liver diseases and may prolong the survival time of patients in the near future.
Research articles
Two less common human microRNAs miR-875 and miR-3144 target a conserved site of E6 oncogene in most high-risk human papillomavirus subtypes
Lin Lin, Qingqing Cai, Xiaoyan Zhang, Hongwei Zhang, Yang Zhong, Congjian Xu, Yanyun Li
2015, 6(8): 575-588. doi: 10.1007/s13238-015-0142-8
Human papillomaviruses (HPVs) including high-risk (HR) and low-risk (LR) subtypes have distinguishable variation on both genotypes and phenotypes. The coinfection of multiple HR-HPVs, headed by HPV16, is common in cervical cancer in female. Recently accumulating reports have focused on the interaction between virus and host, particularly the role of human microRNAs (miRNAs) in anti-viral defense by targeting viral genome. Here, we found a well-conserved target site of miRNAs in the genomes of most HR-HPVs, not LR-HPVs, by scanning all potential target sites of human miRNAs on 24 HPVs of unambiguous subtypes of risk. The site is targeted by two less common human miRNAs, miR-875 and miR-3144, and is located in E6 oncogene open reading frame (ORF) and overlap with the first alternative splice exon of viral early transcripts. In validation tests, miR-875 and miR-3144 were identified to suppress the target reporter activity markedly and inhibit the expression of both synthetically exogenous E6 and endogenous E6 oncogene. High level of two miRNAs can inhibit cell growth and promote apoptosis in HPV16-positive cervical cancer cells. This study provides a promising common target of miRNAs for most HR-HPVs and highlights the effects of two low expressed human miRNAs on tumour suppression.
Involvement of collagen-binding heat shock protein 47 in scleroderma-associated fibrosis
Haiyan Chu, Ting Wu, Wenyu Wu, Wenzhen Tu, Shuai Jiang, Sidi Chen, Yanyun Ma, Qingmei Liu, Xiaodong Zhou, Li Jin, Jiucun Wang
2015, 6(8): 589-598. doi: 10.1007/s13238-015-0171-3
Uncontrolled fibrosis of skin and internal organs is the main characteristic of scleroderma, and collagen is a major extracellular matrix protein that deposits in the fibrotic organs. As the chaperone of collagen, heat shock protein 47 (HSP47) is closely related with the development of fibrosis. To explore the potential function of HSP47 in the pathogenesis of scleroderma, the clinical, in vivo and in vitro studies were performed. In clinical, the increased mRNA level of HSP47 was observed in the skin fibroblasts and PBMC from scleroderma patients, and the enhanced protein level of HSP47 was also detected in the skin biopsy and plasma of the above patients. Unexpectedly, the enhanced levels of HSP47 were positively correlated with the presence of anti-centromere antibody in scleroderma patients. Moreover, a high expression of HSP47 was found in the skin lesion of BLM-induced scleroderma mouse model. Further in vitro studies demonstrated that HSP47 knockdown could block the intracellular and extracellular collagen over-productions induced by exogenous TGF-β. Therefore, the results in this study provide direct evidence that HSP47 is involved in the pathogenesis of scleroderma. The high expression of HSP47 can be detected in the circulatory system of scleroderma patients, indicating that HSP47 may become a pathological marker to assess the progression of scleroderma, and also explain the systemic fibrosis of scleroderma. Meanwhile, collagen over-expression is blocked by HSP47 knockdown, suggesting the possibility that HSP47 can be a potential therapeutic target for scleroderma.
LSY-2 is essential for maintaining the germ-soma distinction in C. elegans
Long Lin, Yuping Li, Libo Yan, Gangming Zhang, Yu Zhao, Hong Zhang
2015, 6(8): 599-609. doi: 10.1007/s13238-015-0173-1
The mechanisms that specify and maintain the characteristics of germ cells during animal development are poorly understood. In this study, we demonstrated that loss of function of the zinc-finger gene lsy-2 results in various somatic cells adopting germ cells characteristics, including expression of germline-specific P granules, enhanced RNAi activity and transgene silencing. The soma to germ transformation in lsy-2 mutants requires the activities of multiple chromatin remodeling complexes, including the MES-4 complex and the ISW-1 complex. The distinct germline-specific features in somatic cells and the gene expression profile indicate that lsy-2 acts in the Mec complex in this process. Our study demonstrated that lsy-2 functions in the maintenance of the soma-germ distinction.
Landscape of protein domain interactome
Ting Zhang, Shuang Li, Wei Zuo
2015, 6(8): 610-614. doi: 10.1007/s13238-015-0158-0
The structure of WbnH in a near active state
Fengzhi Li, Siwei Li, Xiaofen Liu, Xue Yang, Peng Wang, Yuequan Shen
2015, 6(8): 615-618. doi: 10.1007/s13238-015-0151-7
Determining structural ensembles of flexible multi-domain proteins using small-angle X-ray scattering and molecular dynamics simulations
Yonghui Zhang, Bin Wen, Junhui Peng, Xiaobing Zuo, Qingguo Gong, Zhiyong Zhang
2015, 6(8): 619-623. doi: 10.1007/s13238-015-0162-4