2016 Vol. 7(3)

Dr. Wu Lien Teh, plague fighter and father of the Chinese public health system
Zhongliang Ma, Yanli Li
2016, 7(3): 157-158. doi: 10.1007/s13238-015-0238-1
Role of Notch signaling in regulating innate immunity and inflammation in health and disease
Yingli Shang, Sinead Smith, Xiaoyu Hu
2016, 7(3): 159-174. doi: 10.1007/s13238-016-0250-0
The Notch signaling pathway is conserved from Drosophila to mammals and is critically involved in developmental processes. In the immune system, it has been established that Notch signaling regulates multiple steps of T and B cell development in both central and peripheral lymphoid organs. Relative to the well documented role of Notch signaling in lymphocyte development, less is known about its role in regulating myeloid lineage development and function, especially in the context of acute and chronic inflammation. In this review article, we will describe the evidence accumulated during the recent years to support a key regulatory role of the Notch pathway in innate immune and inflammatory responses and discuss the potential implications of such regulation for pathogenesis and therapy of inflammatory disorders.
Research articles
Coupled electrophysiological recording and single cell transcriptome analyses revealed molecular mechanisms underlying neuronal maturation
Xiaoying Chen, Kunshan Zhang, Liqiang Zhou, Xinpei Gao, Junbang Wang, Yinan Yao, Fei He, Yuping Luo, Yongchun Yu, Siguang Li, Liming Cheng, Yi E. Sun
2016, 7(3): 175-186. doi: 10.1007/s13238-016-0247-8
The mammalian brain is heterogeneous, containing billions of neurons and trillions of synapses forming various neural circuitries, through which sense, movement, thought, and emotion arise. The cellular heterogeneity of the brain has made it difficult to study the molecular logic of neural circuitry wiring, pruning, activation, and plasticity, until recently, transcriptome analyses with single cell resolution makes decoding of gene regulatory networks underlying aforementioned circuitry properties possible. Here we report success in performing both electrophysiological and whole-genome transcriptome analyses on single human neurons in culture. Using Weighted Gene Coexpression Network Analyses (WGCNA), we identified gene clusters highly correlated with neuronal maturation judged by electrophysiological characteristics. A tight link between neuronal maturation and genes involved in ubiquitination and mitochondrial function was revealed. Moreover, we identified a list of candidate genes, which could potentially serve as biomarkers for neuronal maturation. Coupled electrophysiological recording and single cell transcriptome analysis will serve as powerful tools in the future to unveil molecular logics for neural circuitry functions.
Structural dynamics of the yeast ShwachmanDiamond syndrome protein (Sdo1) on the ribosome and its implication in the 60S subunit maturation
Chengying Ma, Kaige Yan, Dan Tan, Ningning Li, Yixiao Zhang, Yi Yuan, Zhifei Li, Meng-Qiu Dong, Jianlin Lei, Ning Gao
2016, 7(3): 187-200. doi: 10.1007/s13238-015-0242-5
The human Shwachman-Diamond syndrome (SDS) is an autosomal recessive disease caused by mutations in a highly conserved ribosome assembly factor SBDS. The functional role of SBDS is to cooperate with another assembly factor, elongation factor 1-like (Efl1), to promote the release of eukaryotic initiation factor 6 (eIF6) from the late-stage cytoplasmic 60S precursors. In the present work, we characterized, both biochemically and structurally, the interaction between the 60S subunit and SBDS protein (Sdo1p) from yeast. Our data show that Sdo1p interacts tightly with the mature 60S subunit in vitro through its domain I and Ⅱ, and is capable of bridging two 60S subunits to form a stable 2:2 dimer. Structural analysis indicates that Sdo1p bind to the ribosomal P-site, in the proximity of uL16 and uL5, and with direct contact to H69 and H38. The dynamic nature of Sdo1p on the 60S subunit, together with its strategic binding position, suggests a surveillance role of Sdo1p in monitoring the conformational maturation of the ribosomal P-site. Altogether, our data support a conformational signal-relay cascade during late-stage 60S maturation, involving uL16, Sdo1p, and Efl1p, which interrogates the functional P-site to control the departure of the anti-association factor eIF6.
RBP-J is required for M2 macrophage polarization in response to chitin and mediates expression of a subset of M2 genes
Julia Foldi, Yingli Shang, Baohong Zhao, Lionel B. Ivashkiv, Xiaoyu Hu
2016, 7(3): 201-209. doi: 10.1007/s13238-016-0248-7
Development of alternatively activated (M2) macrophage phenotypes is a complex process that is coordinately regulated by a plethora of pathways and factors. Here, we report that RBP-J, a DNA-binding protein that integrates signals from multiple pathways including the Notch pathway, is critically involved in polarization of M2 macrophages. Mice deficient in RBP-J in the myeloid compartment exhibited impaired M2 phenotypes in vivo in a chitin-induced model of M2 polarization. Consistent with the in vivo findings, M2 polarization was partially compromised in vitro in Rbpj-deficient macrophages as demonstrated by reduced expression of a subset of M2 effector molecules including arginase 1. Functionally, myeloid Rbpj deficiency impaired M2 effector functions including recruitment of eosinophils and suppression of T cell proliferation. Collectively, we have identified RBPJ as an essential regulator of differentiation and function of alternatively activated macrophages.
Modeling xeroderma pigmentosum associated neurological pathologies with patients-derived iPSCs
Lina Fu, Xiuling Xu, Ruotong Ren, Jun Wu, Weiqi Zhang, Jiping Yang, Xiaoqing Ren, Si Wang, Yang Zhao, Liang Sun, Yang Yu, Zhaoxia Wang, Ze Yang, Yun Yuan, Jie Qiao, Juan Carlos Izpisua Belmonte, Jing Qu, Guang-Hui Liu
2016, 7(3): 210-221. doi: 10.1007/s13238-016-0244-y
Xerorders caused by mutations of XP-associated genes, resulting in impairment of DNA repair. XP patients frequently exhibit neurological degeneration, but the underlying mechanism is unknown, in part due to lack of proper disease models. Here, we generated patientspecific induced pluripotent stem cells (iPSCs) harboring mutations in five different XP genes including XPA, XPB, XPC, XPG, and XPV. These iPSCs were further differentiated to neural cells, and their susceptibility to DNA damage stress was investigated. Mutation of XPA in either neural stem cells (NSCs) or neurons resulted in severe DNA damage repair defects, and these neural cells with mutant XPA were hyper-sensitive to DNA damage-induced apoptosis. Thus, XP-mutant neural cells represent valuable tools to clarify the molecular mechanisms of neurological abnormalities in the XP patients.
The BAH domain of BAHD1 is a histone H3K27me3 reader
Dan Zhao, Xiaojie Zhang, Haipeng Guan, Xiaozhe Xiong, Xiaomeng Shi, Haiteng Deng, Haitao Li
2016, 7(3): 222-226. doi: 10.1007/s13238-016-0243-z
Three-dimensional visualization of arsenic stimulated mouse liver sinusoidal by FIB-SEM approach
Wenbo Li, Wei Ding, Gang Ji, Li Wang, Jianguo Zhang, Fei Sun
2016, 7(3): 227-232. doi: 10.1007/s13238-016-0246-9

Current Issue

March, 2019

Volume 10, Issue 3

Pages 157-233

About the cover

Metastasis is the leading cause of human cancer deaths.Unfortunately, no approved drugs are available for antimetastatic treatment. In this study, high-throughputsequencing-based high-throughput screening (HTS2) anda breast cancer lung metastasis (BCLM)-associated genesignature were combined to discover anti-metastatic drugs.After screening of thousands of compounds, Shao et al.identifed Ponatinib as a BCLM inhibitor. Ponatinib signifcantlyinhibited the migration and mammosphere formation of breastcancer cells in vitro and blocked BCLM in multiple mousemodels. This study may facilitate the therapeutic treatment ofBCLM as well as other metastases.

Institute of Biophysics, Chinese Academy of Sciences, 15 Datun Road, Chaoyang Beijing 100101, China

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