Latest Articles

The role of telomere-binding modulators in pluripotent stem cells
Feng Li, Yuanlong Ge, Dan Liu, Zhou Songyang
 doi: 10.1007/s13238-019-0651-y
Pluripotent stem cells (PSCs) such as embryonic stem cells (ESCs), ESCs derived by somatic cell nuclear transfer (ntESCs), and induced pluripotent stem cells (iPSCs) have unlimited capacity for self-renewal and pluripotency and can give rise to all types of somatic cells. In order to maintain their self-renewal and pluripotency, PSCs need to preserve their telomere length and homeostasis. In recent years, increasing studies have shown that telomere reprogramming is essential for stem cell pluripotency maintenance and its induced pluripotency process. Telomere-associated proteins are not only required for telomere maintenance in both stem cells, their extra-telomeric functions have also been found to be critical as well. Here, we will discuss how telomeres and telomere-associated factors participate and regulate the maintenance of stem cell pluripotency.
Correction to: Inhibition of p53 and/or AKT as a new therapeutic approach specifically targeting ALT cancers
Yuanlong Ge, Shu Wu, Zepeng Zhang, Xiaocui Li, Feng Li, Siyu Yan, Haiying Liu, Junjiu Huang, Yong Zhao
 doi: 10.1007/s13238-019-0640-1
Continuous culture of urine-derived bladder cancer cells for precision medicine
Shuai Jiang, Jiaqi Wang, Chen Yang, Renke Tan, Jun Hou, Yuan Shi, Huihui Zhang, Shiyu Ma, Jianan Wang, Mengmeng Zhang, George Philips, Zengxia Li, Jian Ma, Wanjun Yu, Guohua Wang, Yuanming Wu, Richard Schlegel, Huina Wang, Shanbo Cao, Jianming Guo, Xuefeng Liu, Yongjun Dang
 doi: 10.1007/s13238-019-0649-5
FBXW7 E3 ubiquitin ligase: degrading, not degrading, or being degraded
Huiyin Lan, Yi Sun
 doi: 10.1007/s13238-019-0652-x
Low-dose quercetin positively regulates mouse healthspan
Lingling Geng, Zunpeng Liu, Si Wang, Shuhui Sun, Shuai Ma, Xiaoqian Liu, Piu Chan, Liang Sun, Moshi Song, Weiqi Zhang, Guang-Hui Liu, Jing Qu
 doi: 10.1007/s13238-019-0646-8
Inhibition of Rac1-dependent forgetting alleviates memory deficits in animal models of Alzheimer's disease
Wenjuan Wu, Shuwen Du, Wei Shi, Yunlong Liu, Ying Hu, Zuolei Xie, Xinsheng Yao, Zhenyu Liu, Weiwei Ma, Lin Xu, Chao Ma, Yi Zhong
 doi: 10.1007/s13238-019-0641-0
Accelerated forgetting has been identified as a feature of Alzheimer's disease (AD), but the therapeutic efficacy of the manipulation of biological mechanisms of forgetting has not been assessed in AD animal models. Ras-related C3 botulinum toxin substrate 1 (Rac1), a small GTPase, has been shown to regulate active forgetting in Drosophila and mice. Here, we showed that Rac1 activity is aberrantly elevated in the hippocampal tissues of AD patients and AD animal models. Moreover, amyloid-beta 42 could induce Rac1 activation in cultured cells. The elevation of Rac1 activity not only accelerated 6-hour spatial memory decay in 3-month-old APP/PS1 mice, but also significantly contributed to severe memory loss in aged APP/PS1 mice. A similar age-dependent Rac1 activity-based memory loss was also observed in an AD fly model. Moreover, inhibition of Rac1 activity could ameliorate cognitive defects and synaptic plasticity in AD animal models. Finally, two novel compounds, identified through behavioral screening of a randomly selected pool of brain permeable small molecules for their positive effect in rescuing memory loss in both fly and mouse models, were found to be capable of inhibiting Rac1 activity. Thus, multiple lines of evidence corroborate in supporting the idea that inhibition of Rac1 activity is effective for treating AD-related memory loss.
Long non-coding RNA LncKdm2b regulates cortical neuronal differentiation by cis-activating Kdm2b
Wei Li, Wenchen Shen, Bo Zhang, Kuan Tian, Yamu Li, Lili Mu, Zhiyuan Luo, Xiaoling Zhong, Xudong Wu, Ying Liu, Yan Zhou
 doi: 10.1007/s13238-019-0650-z
The mechanisms underlying spatial and temporal control of cortical neurogenesis of the brain are largely elusive. Long non-coding RNAs (lncRNAs) have emerged as essential cell fate regulators. Here we found LncKdm2b (also known as Kancr), a lncRNA divergently transcribed from a bidirectional promoter of Kdm2b, is transiently expressed during early differentiation of cortical projection neurons. Interestingly, Kdm2b's transcription is positively regulated in cis by LncKdm2b, which has intrinsic-activating function and facilitates a permissive chromatin environment at the Kdm2b's promoter by associating with hnRNPAB. Lineage tracing experiments and phenotypic analyses indicated LncKdm2b and Kdm2b are crucial in proper differentiation and migration of cortical projection neurons. These observations unveiled a lncRNA-dependent machinery in regulating cortical neuronal differentiation.
Core transcriptional signatures of phase change in the migratory locust
Pengcheng Yang, Li Hou, Xianhui Wang, Le Kang
 doi: 10.1007/s13238-019-0648-6
Phenotypic plasticity plays fundamental roles in successful adaptation of animals in response to environmental variations. Here, to reveal the transcriptome reprogramming in locust phase change, a typical phenotypic plasticity, we conducted a comprehensive analysis of multiple phase-related transcriptomic datasets of the migratory locust. We defined PhaseCore genes according to their contribution to phase differentiation by the adjustment for confounding principal components analysis algorithm (AC-PCA). Compared with other genes, PhaseCore genes predicted phase status with over 87.5% accuracy and displayed more unique gene attributes including the faster evolution rate, higher CpG content and higher specific expression level. Then, we identified 20 transcription factors (TFs) named PhaseCoreTF genes that are associated with the regulation of PhaseCore genes. Finally, we experimentally verified the regulatory roles of three representative TFs (Hr4, Hr46, and grh) in phase change by RNAi. Our findings revealed that core transcriptional signatures are involved in the global regulation of locust phase changes, suggesting a potential common mechanism underlying phenotypic plasticity in insects. The expression and network data are accessible in an online resource called LocustMine (
Tissue-resident memory-like ILCs: innate counterparts of TRM cells
Xianwei Wang, Zhigang Tian, Hui Peng
 doi: 10.1007/s13238-019-0647-7
Innate lymphoid cells (ILCs) are defined as lymphocytes that lack RAG recombinase and do not express diverse antigen receptors; however, recent studies have revealed the adaptive features of ILCs. Mouse cytomegalovirus (MCMV)-and cytokine-induced memory natural killer (NK) cells circulate in the blood and are referred to as conventional memory NK cells. In contrast, virusand hapten-induced memory NK cells, hapten-induced memory ILC1s, and cytokine-induced memory-like ILC2s exhibit long-term residency in the liver or lung, and are referred to as tissue-resident memory ILCs. Considering their similar migration patterns and memory potential, tissue-resident memory ILCs could be regarded as innate counterparts of resident memory T (TRM) cells. Both tissue-resident memory ILCs and TRM cells share common characteristics in terms of dynamics, phenotype, and molecular regulation. The emergence of ILC memory expands the basic biology of ILCs and prompts us to re-examine their functions in disease progression. This review discusses the evidence supporting tissue-resident memory NK cells and other memory ILC subsets, compares them with TRM cells, and highlights key unsolved questions in this emerging field.
Ubiquitin is double-phosphorylated by PINK1 for enhanced pH-sensitivity of conformational switch
Shang-Xiang Ye, Zhou Gong, Ju Yang, Yu-Xin An, Zhu Liu, Qun Zhao, Ewen Lescop, Xu Dong, Chun Tang
 doi: 10.1007/s13238-019-0644-x
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
The evolving CRISPR technology
Meng Yan, Jinsong Li
 doi: 10.1007/s13238-019-0645-9
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
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.
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.
CRISPR-mediated gene editing to rescue haploinsufficient obesity syndrome
Zhifeng Wang, Liu Yang, Shen Qu, Chao Zhang
 doi: 10.1007/s13238-019-0635-y
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.
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.
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.
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
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
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
Richang Cao: pioneer advocate of dialectical materialism applied to psychological research
Baoyuan Zhang
 doi: 10.1007/s13238-019-0615-2
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.
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
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
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
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
Professor Li-Pin. King: a famous physiologist in China
Wei Gong, Fangfang Wang, Yike Ying
 doi: 10.1007/s13238-018-0582-z
Shitsan Pai: the establishment of the first biophysics department in the world
Rui Liu
 doi: 10.1007/s13238-018-0557-0
Zing-Yang Kuo and behavior epigenesis based on animal experiments
Yanyan Qian, Wei Chen, Benyu Guo
 doi: 10.1007/s13238-018-0516-9
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
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
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
Shu-szi Sin: A Chinese pioneer biologist, ancient agronomist, and educator
Qun Xie, Yan-ping Cheng, Lei Fu
 doi: 10.1007/s13238-019-00657-x
A pioneer of modern Chinese Physiology: Dr. Robert Kho-Seng Lim
Fang Zhang
 doi: 10.1007/s13238-019-00655-z
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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