Latest Articles

Mitochondrion-processed TERC regulates senescence without affecting telomerase activities
Qian Zheng, Peipei Liu, Ge Gao, Jiapei Yuan, Pengfeng Wang, Jinliang Huang, Leiming Xie, Xinping Lu, Fan Di, Tanjun Tong, Jun Chen, Zhi Lu, Jisong Guan, Geng Wang
 doi: 10.1007/s13238-019-0612-5
Mitochondrial dysfunctions play major roles in ageing. How mitochondrial stresses invoke downstream responses and how specificity of the signaling is achieved, however, remains unclear. We have previously discovered that the RNA component of Telomerase TERC is imported into mitochondria, processed to a shorter form TERC-53, and then exported back to the cytosol. Cytosolic TERC-53 levels respond to mitochondrial functions, but have no direct effect on these functions, suggesting that cytosolic TERC-53 functions downstream of mitochondria as a signal of mitochondrial functions. Here, we show that cytosolic TERC-53 plays a regulatory role on cellular senescence and is involved in cognition decline in 10 months old mice, independent of its telomerase function. Manipulation of cytosolic TERC-53 levels affects cellular senescence and cognition decline in 10 months old mouse hippocampi without affecting telomerase activity, and most importantly, affects cellular senescence in terc-/- cells. These findings uncover a senescence-related regulatory pathway with a non-coding RNA as the signal in mammals.
RETRACTED ARTICLE: DDB1 and Cul4 are necessary for gene silencing and heterochromatin formation at pericentromeric regions in Neurospora
Yingqiong Cao, Jicheng Wei, Silu Yang, Jinquan Sun, Hui Xu, Ying Wang, Yuanbiao Zhao, Qun He
 doi: 10.1007/s13238-014-0067-7
PCGF6 regulates stem cell pluripotency as a transcription activator via super-enhancer dependent chromatin interactions
Xiaona Huang, Chao Wei, Fenjie Li, Lumeng Jia, Pengguihang Zeng, Jiahe Li, Jin Tan, Tuanfeng Sun, Shaoshuai Jiang, Jia Wang, Xiuxiao Tang, Qingquan Zhao, Bin Liu, Limin Rong, Cheng Li, Junjun Ding
 doi: 10.1007/s13238-019-0629-9
Polycomb group (PcG) ring finger protein 6 (PCGF6), though known as a member of the transcription-repressing complexes, PcG, also has activation function in regulating pluripotency gene expression. However, the mechanism underlying the activation function of PCGF6 is poorly understood. Here, we found that PCGF6 co-localizes to gene activation regions along with pluripotency factors such as OCT4. In addition, PCGF6 was recruited to a subset of the super-enhancer (SE) regions upstream of cell cycle-associated genes by OCT4, and increased their expression. By combining with promoter capture Hi-C data, we found that PCGF6 activates cell cycle genes by regulating SE-promoter interactions via 3D chromatin. Our findings highlight a novel mechanism of PcG protein in regulating pluripotency, and provide a research basis for the therapeutic application of pluripotent stem cells.
Correction to: Prof. Huan-Yong Chen: a leading botanist and taxonomist, one of the pioneers and founders of modern plant taxonomy in China
Rui-Lan Huang
 doi: 10.1007/s13238-018-0569-9
Crystal structure of Lamellipodin implicates diverse functions in actin polymerization and Ras signaling
Yu-Chung Chang, Hao Zhang, Mark L. Brennan, Jinhua Wu
 doi: 10.1007/s13238-012-2082-x
The adapter protein Lamellipodin (Lpd) plays an important role in cell migration. In particular, Lpd mediates lamellipodia formation by regulating actin dynamics via interacting with Ena/VASP proteins. Its RA-PH tandem domain configuration suggests that like its paralog RIAM, Lpd may also mediate particular Ras GTPase signaling. We determined the crystal structures of the Lpd RA-PH domains alone and with an N-terminal coiled-coil region (cc-RA-PH). These structures reveal that apart from the anticipated coiled-coil interaction, Lpd may also oligomerize through a second intermolecular contact site. We then validated both oligomerization interfaces in solution by mutagenesis. A fluorescence-polarization study demonstrated that Lpd binds phosphoinositol with low affinity. Based on our crystallographic and biochemical data, we propose that Lpd and RIAM serve diverse functions:Lpd plays a predominant role in regulating actin polymerization, and its function in mediating Ras GTPase signaling is largely suppressed compared to RIAM.
Modeling neuropsychiatric disorders using human induced pluripotent stem cells
Meiyan Wang, Lei Zhang, Fred H. Gage
 doi: 10.1007/s13238-019-0638-8
Neuropsychiatric disorders are complex disorders characterized by heterogeneous genetic variations, variable symptoms, and widespread changes in anatomical pathology. In the context of neuropsychiatric disorders, limited access to relevant tissue types presents challenges for understanding disease etiology and developing effective treatments. Induced pluripotent stem cells (iPSCs) reprogrammed from patient somatic cells offer an opportunity to recapitulate disease development in relevant cell types, and they provide novel approaches for understanding disease mechanisms and for development of effective treatments. Here we review recent progress and challenges in differentiation paradigms for generating disease-relevant cells and recent studies of neuropsychiatric disorders using human pluripotent stem cell (hPSC) models where cellular phenotypes linked to disease have been reported. The use of iPSC-based disease models holds great promise for understanding disease mechanisms and supporting discovery of effective treatments.
The evolving CRISPR technology
Meng Yan, Jinsong Li
 doi: 10.1007/s13238-019-0645-9
Cells derived from iPSC can be immunogenic-Yes or No?
Jiani Cao, Xiaoyan Li, Xiao Lu, Chao Zhang, Honghao Yu, Tongbiao Zhao
 doi: 10.1007/s13238-013-3909-9
The induced pluripotent stem cells (iPSCs), derived by ectopic expression of reprogramming factors in somatic cells, can potentially provide unlimited autologous cells for regenerative medicine. In theory, the autologous cells derived from patient iPSCs should be immune tolerant by the host without any immune rejections. However, our recent studies have found that even syngeneic iPSC-derived cells can be immunogenic in syngeneic hosts by using a teratoma transplantation model (Zhao et al., 2011). Recently two research groups differentiated the iPSCs into different germ layers or cells, transplanted those cells to the syngeneic hosts, and evaluated the immunogenicity of those cells. Both of the two studies support our conclusions that some certain but not all tissues derived from iPSCs can be immunogenic, although they claimed either "negligible" or "lack of" immunogenicity in iPSC derivatives (Araki et al., 2013; Guha et al., 2013). To test the immunogenicity of clinically valuable cells differentiated from human iPSCs are emergently required for translation of iPSC technology to clinics.
Structural insights into the species preference of the influenza B virus NS1 protein in ISG15 binding
Yinan Jiang, Xinquan Wang
 doi: 10.1007/s13238-018-0598-4
Richang Cao: pioneer advocate of dialectical materialism applied to psychological research
Baoyuan Zhang
 doi: 10.1007/s13238-019-0615-2
Propofol reduces synaptic strength by inhibiting sodium and calcium channels at nerve terminals
Qing-Zhuo Liu, Mei Hao, Zi-Yang Zhou, Jian-Long Ge, Yi-Chen Wu, Ling-Ling Zhao, Xiang Wu, Yi Feng, Hong Gao, Shun Li, Lei Xue
 doi: 10.1007/s13238-019-0624-1
Zing-Yang Kuo and behavior epigenesis based on animal experiments
Yanyan Qian, Wei Chen, Benyu Guo
 doi: 10.1007/s13238-018-0516-9
Targeting tissue-specific metabolic signaling pathways in aging: the promise and limitations
Fang Hu, Feng Liu
 doi: 10.1007/s13238-013-3077-y
It has been well established that most of the age-related diseases such as insulin resistance, type 2 diabetes, hypertension, cardiovascular disease, osteoporosis, and atherosclerosis are all closely related to metabolic dysfunction. On the other hand, interventions on metabolism such as calorie restriction or genetic manipulations of key metabolic signaling pathways such as the insulin and mTOR signaling pathways slow down the aging process and improve healthy aging. These findings raise an important question as to whether improving energy homeostasis by targeting certain metabolic signaling pathways in specific tissues could be an effective anti-aging strategy. With a more comprehensive understanding of the tissuespecific roles of distinct metabolic signaling pathways controlling energy homeostasis and the cross-talks between these pathways during aging may lead to the development of more effective therapeutic interventions not only for metabolic dysfunction but also for aging.
Histone deacetylase 6 and cytoplasmic linker protein 170 function together to regulate the motility of pancreatic cancer cells
Dengwen Li, Xiaodong Sun, Linlin Zhang, Bing Yan, Songbo Xie, Ruming Liu, Min Liu, Jun Zhou
 doi: 10.1007/s13238-013-3098-6
Pancreatic cancer is a devastating disease with the worst prognosis among all the major human malignancies. The propensity to rapidly metastasize contributes significantly to the highly aggressive feature of pancreatic cancer. The molecular mechanisms underlying this remain elusive, and proteins involved in the control of pancreatic cancer cell motility are not fully characterized. In this study, we find that histone deacetylase 6 (HDAC6), a member of the class Ⅱ HDAC family, is highly expressed at both protein and mRNA levels in human pancreatic cancer tissues. HDAC6 does not obviously affect pancreatic cancer cell proliferation or cell cycle progression. Instead, it significantly promotes the motility of pancreatic cancer cells. Further studies reveal that HDAC6 interacts with cytoplasmic linker protein 170 (CLIP-170) and that these two proteins function together to stimulate the migration of pancreatic cancer cells. These findings provide mechanistic insight into the progression of pancreatic cancer and suggest HDAC6 as a potential target for the management of this malignancy.
Shitsan Pai: the establishment of the first biophysics department in the world
Rui Liu
 doi: 10.1007/s13238-018-0557-0
Retraction Note to: DDB1 and Cul4 are necessary for gene silencing and heterochromatin formation at pericentromeric regions in Neurospora
Yingqiong Cao, Jicheng Wei, Silu Yang, Jinquan Sun, Hui Xu, Ying Wang, Yuanbiao Zhao, Qun He
 doi: 10.1007/s13238-014-0079-3
Colonization process of Arabidopsis thaliana roots by a green fluorescent protein-tagged isolate of Verticillium dahliae
Pan Zhao, Yun-Long Zhao, Yun Jin, Tao Zhang, Hui-Shan Guo
 doi: 10.1007/s13238-013-3061-6
Chimeric antigen receptor T (CAR-T) cells expanded with IL-7/IL-15 mediate superior antitumor effects
Jianxia Zhou, Liyuan Jin, Fuping Wang, Yuan Zhang, Bing Liu, Tongbiao Zhao
 doi: 10.1007/s13238-019-0643-y
DNA-dependent protein kinase catalytic subunit (DNA-PKcs) contributes to incorporation of histone variant H2A.Z into nucleosomes
Ling-Yao Wang, Yun-xiao He, Min Li, Jian Ding, Yi Sui, Joan W. Conaway, Ronald C. Conaway, Fei Wang, Jingji Jin, Yong Cai
 doi: 10.1007/s13238-019-0632-1
Jiao Shao: A forerunner of physiological psychology and comparative psychology in China
Lijun Wang, Yanyan Qian, Yanjie Su
 doi: 10.1007/s13238-018-0592-x
Tonghua Liu: A life dedicated to clinical pathology
Lin Dong, Tanping Fu, Junyi Pang, Zhiyong Liang, Wenli Duan
 doi: 10.1007/s13238-018-0601-0
Analysis of VISTA expression and function in renal cell carcinoma highlights VISTA as a potential target for immunotherapy
Shanjuan Hong, Qing Yuan, Haizhui Xia, Genzhen Zhu, Yu Feng, Qiang Wang, Zhiyin Zhang, Wei He, Jian Lu, Chen Dong, Ling Ni
 doi: 10.1007/s13238-019-0642-z
IL-2 and IL-15 dependent thymic development of Foxp3-expressing regulatory T lymphocytes
Cécile Apert, Paola Romagnoli, Joost P. M. van Meerwijk
 doi: 10.1007/s13238-017-0425-3
Immunosuppressive regulatory T lymphocytes (Treg) expressing the transcription factor Foxp3 play a vital role in the maintenance of tolerance of the immunesystem to self and innocuous non-self. Most Treg that are critical for the maintenance of tolerance to self, develop as an independent T-cell lineage from common T cell precursors in the thymus. In this organ, their differentiation requires signals from the T cell receptor for antigen, from co-stimulatory molecules, as well as from cytokine-receptors. Here we focus on the cytokines implicated in thymic development of Treg, with a particular emphasis on the roles of interleukin-2 (IL-2) and IL-15. The more recently appreciated involvement of TGF-β in thymic Treg development is also briefly discussed. Finally, we discuss how cytokine-dependence of Treg development allows for temporal, quantitative, and potentially qualitative modulation of this process.
Crystal structure and function of Rbj: A constitutively GTP-bound small G protein with an extra DnaJ domain
Zhengrong Gao, Keke Xing, Chang Zhang, Jianxun Qi, Liang Wang, Shan Gao, Ren Lai
 doi: 10.1007/s13238-019-0622-3
Correction to: Gene activation in human cells using CRISPR/Cpf1-p300 and CRISPR/Cpf1-SunTag systems
Xin Zhang, Wei Wang, Lin Shan, Le Han, Shufeng Ma, Yan Zhang, Bingtao Hao, Ying Lin, Zhili Rong
 doi: 10.1007/s13238-018-0585-9
Neddylation inhibitor MLN4924 suppresses cilia formation by modulating AKT1
Hongmei Mao, Zaiming Tang, Hua Li, Bo Sun, Mingjia Tan, Shaohua Fan, Yuan Zhu, Yi Sun
 doi: 10.1007/s13238-019-0614-3
The primary cilium is a microtubule-based sensory organelle. The molecular mechanism that regulates ciliary dynamics remains elusive. Here, we report an unexpected finding that MLN4924, a small molecule inhibitor of NEDD8-activating enzyme (NAE), blocks primary ciliary formation by inhibiting synthesis/ assembly and promoting disassembly. This is mainly mediated by MLN4924-induced phosphorylation of AKT1 at Ser473 under serum-starved, ciliary-promoting conditions. Indeed, pharmaceutical inhibition (by MK2206) or genetic depletion (via siRNA) of AKT1 rescues MLN4924 effect, indicating its causal role. Interestingly, pAKT1-Ser473 activity regulates both ciliary synthesis/ assembly and disassembly in a MLN4924 dependent manner, whereas pAKT-Thr308 determines the ciliary length in MLN4924-independent but VHL-dependent manner. Finally, MLN4924 inhibits mouse hair regrowth, a process requires ciliogenesis. Collectively, our study demonstrates an unexpected role of a neddylation inhibitor in regulation of ciliogenesis via AKT1, and provides a proof-of-concept for potential utility of MLN4924 in the treatment of human diseases associated with abnormal ciliogenesis.
Retraction Note: Cryptomycota: the missing link
Krishna Bolla, Elizabeth Jane Ashforth
 doi: 10.1007/s13238-012-2820-0
Current advances in haploid stem cells
Tongtong Cui, Zhikun Li, Qi Zhou, Wei Li
 doi: 10.1007/s13238-019-0625-0
Diploidy is the typical genomic mode in all mammals. Haploid stem cells are artificial cell lines experimentally derived in vitro in the form of different types of stem cells, which combine the characteristics of haploidy with a broad developmental potential and open the possibility to uncover biological mysteries at a genomic scale. To date, a multitude of haploid stem cell types from mouse, rat, monkey and humans have been derived, as more are in development. They have been applied in high-throughput genetic screens and mammalian assisted reproduction. Here, we review the generation, unique properties and broad applications of these remarkable cells.
Correction to: Developing potent PROTACs tools for selective degradation of HDAC6 protein
Zixuan An, Wenxing Lv, Shang Su, Wei Wu, Yu Rao
 doi: 10.1007/s13238-019-0613-4
Professor Yongjia Duan: a distinguished plant pathologist and agricultural educator
Fei Du, Wei-Ping Deng, Xia-Hong He, Hong Cai, You-Yong Zhu
 doi: 10.1007/s13238-019-0616-1
Professor Cuifen Huang: a great molecular geneticist and the founder of genetic engineering in China
Wei Gong, Leyi Cui, Yike Ying, Yijing Shen, Jiaqi Bao
 doi: 10.1007/s13238-019-0620-5
Rescue of premature aging defects in Cockayne syndrome stem cells by CRISPR/ Cas9-mediated gene correction
Si Wang, Zheying Min, Qianzhao Ji, Lingling Geng, Yao Su, Zunpeng Liu, Huifang Hu, Lixia Wang, Weiqi Zhang, Keiichiro Suzuiki, Yu Huang, Puyao Zhang, Tie-Shan Tang, Jing Qu, Yang Yu, Guang-Hui Liu, Jie Qiao
 doi: 10.1007/s13238-019-0623-2
Cockayne syndrome (CS) is a rare autosomal recessive inherited disorder characterized by a variety of clinical features, including increased sensitivity to sunlight, progressive neurological abnormalities, and the appearance of premature aging. However, the pathogenesis of CS remains unclear due to the limitations of current disease models. Here, we generate integration-free induced pluripotent stem cells (iPSCs) from fibroblasts from a CS patient bearing mutations in CSB/ERCC6 gene and further derive isogenic genecorrected CS-iPSCs (GC-iPSCs) using the CRISPR/Cas9 system. CS-associated phenotypic defects are recapitulated in CS-iPSC-derived mesenchymal stem cells (MSCs) and neural stem cells (NSCs), both of which display increased susceptibility to DNA damage stress. Premature aging defects in CS-MSCs are rescued by the targeted correction of mutant ERCC6. We next map the transcriptomic landscapes in CS-iPSCs and GC-iPSCs and their somatic stem cell derivatives (MSCs and NSCs) in the absence or presence of ultraviolet (UV) and replicative stresses, revealing that defects in DNA repair account for CS pathologies. Moreover, we generate autologous GC-MSCs free of pathogenic mutation under a cGMP (Current Good Manufacturing Practice)-compliant condition, which hold potential for use as improved biomaterials for future stem cell replacement therapy for CS. Collectively, our models demonstrate novel disease features and molecular mechanisms and lay a foundation for the development of novel therapeutic strategies to treat CS.
A 110-year-old wise man: Professor Libin T. Cheng, one of the founders of biochemistry and nutrition in China
He Zhang
 doi: 10.1007/s13238-017-0428-0
Professor Li-Pin. King: a famous physiologist in China
Wei Gong, Fangfang Wang, Yike Ying
 doi: 10.1007/s13238-018-0582-z
Telomere-dependent and telomereindependent roles of RAP1 in regulating human stem cell homeostasis
Xing Zhang, Zunpeng Liu, Xiaoqian Liu, Si Wang, Yiyuan Zhang, Xiaojuan He, Shuhui Sun, Shuai Ma, Ng Shyh-Chang, Feng Liu, Qiang Wang, Xiaoqun Wang, Lin Liu, Weiqi Zhang, Moshi Song, Guang-Hui Liu, Jing Qu
 doi: 10.1007/s13238-019-0610-7
RAP1 is a well-known telomere-binding protein, but its functions in human stem cells have remained unclear. Here we generated RAP1-deficient human embryonic stem cells (hESCs) by using CRISPR/Cas9 technique and obtained RAP1-deficient human mesenchymal stem cells (hMSCs) and neural stem cells (hNSCs) via directed differentiation. In both hMSCs and hNSCs, RAP1 not only negatively regulated telomere length but also acted as a transcriptional regulator of RELN by tuning the methylation status of its gene promoter. RAP1 deficiency enhanced self-renewal and delayed senescence in hMSCs, but not in hNSCs, suggesting complicated lineage-specific effects of RAP1 in adult stem cells.Altogether, these results demonstrate for the first time that RAP1 plays both telomeric and nontelomeric roles in regulating human stem cell homeostasis.
Multiple sgRNAs facilitate base editingmediated i-stop to induce complete and precise gene disruption
Kun Jia, Zongyang Lu, Fei Zhou, Zhiqi Xiong, Rui Zhang, Zhiwei Liu, Yu'e Ma, Lei He, Cong Li, Zhen Zhu, Dejing Pan, Zhengxing Lian
 doi: 10.1007/s13238-019-0611-6
CRISPR-mediated gene editing to rescue haploinsufficient obesity syndrome
Zhifeng Wang, Liu Yang, Shen Qu, Chao Zhang
 doi: 10.1007/s13238-019-0635-y
Phage display screening of therapeutic peptide for cancer targeting and therapy
Phei Er Saw, Er-Wei Song
 doi: 10.1007/s13238-019-0639-7
Recently, phage display technology has been announced as the recipient of Nobel Prize in Chemistry 2018. Phage display technique allows high affinity target-binding peptides to be selected from a complex mixture pool of billions of displayed peptides on phage in a combinatorial library and could be further enriched through the biopanning process; proving to be a powerful technique in the screening of peptide with high affinity and selectivity. In this review, we will first discuss the modifications in phage display techniques used to isolate various cancer-specific ligands by in situ, in vitro, in vivo, and ex vivo screening methods. We will then discuss prominent examples of solid tumor targeting-peptides; namely peptide targeting tumor vasculature, tumor microenvironment (TME) and overexpressed receptors on cancer cells identified through phage display screening. We will also discuss the current challenges and future outlook for targeting peptidebased therapeutics in the clinics.
Systematic biomedical research of the NASA Twins Study facilitates the hazard risk assessment of long-term spaceflight missions
Zhongquan Dai, Xiaohua Lei, Chao Yang, Lei Zhao, Liang Lu, Yinghui Li
 doi: 10.1007/s13238-019-0628-x
Current issue
  • ISSN1674-800X
  • EISSN1674-8018
  • IF (2018) 7.575

Microbiota and Human Health

May 2018
Volume 9
Issue 5
pp: 395-510

Metabolism and Disease

May 2018
Volume 9
Issue 2
pp: 141-237

Therapeutic Antibodies

May 2018
Volume 9
Issue 1
pp: 1-139


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

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