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Regulation of embryonic stem cell self-renewal and differentiation by TGF-β family signaling

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Science china(Life sciences) 2010年第4期53卷 497-503页

作者： FEI Teng & chen ye-{2. The state key laboratory of Biomembrane and Membrane biotechnology, School of Life sciences, tsinghua university, beijing 100084, china 1. The state key {2. of Biomembrane and Membrane biotechnology School of Life Sciences Tsinghua University Beijing 100084 China

Embryonic stem (ES) cells are characterized by their ability to indefinitely self-renew and potential to differentiate into all the cell lineages of the body. ES cells are considered to have potential applications in regenerative medicine. In particular, the emergence of an ES cell analogue-induced pluripotent stem (iPS) cells via somatic cell reprogramming by co-expressing a limited number of critical stemness-related transcriptional factors has solved the problem of obtaining patient-specific pluripotent cells, encouraging researchers to develop more specific and functional cell lineages from ES or iPS cells for broad therapeutic applications. ES cell fate choice is delicately controlled by a core transcriptional network, epigenetic modification profiles and complex signaling cascades both intrinsically and extrinsically. Of these signals, transforming growth factor β (TGF-β) family members, including TGF-β, bone morphogenetic protein (BMP), Activin and Nodal, have been reported to influence cell self-renewal and a broad spectrum of lineage differentiation in ES cells, in accordance with the {2. roles of TGF-β family signaling in early embryo development. In this review, the roles of TGF-β family signals in coordinating ES cell fate determination are summarized.

关键词： embryonic stem cell TGF-β BMP Activin Nodal self-renewal differentiation

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Identification of two distinct transactivation domains in the pluripotency sustaining factor nanog

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Cell Research 2003年第6期13卷 499-502页

作者： guang Jin PAN, DUAN QING PEI Institute of Pharmacology, department of biological sciences and biotechnology and {2. key Labora tory of Biomembrane and Membrane biotechnology, tsinghua Institutes of Biomedicine, tsinghua university, 100084 beijing, china. E-mail: duanqing@aol.comdepartment of Pharmacology, university of Minnesota, Minneapolis, MN55455, USA 1Institute of Pharmacology Department of Biological Sciences and Biotechnology and State Key Laboratory of Biomembrane and Membrane Biotechnology Tsinghua Institutes of Biomedicine Tsinghua University 100084 Beijing China. E-mail: duanqing@*** 2.0} of Pharmacology University of Minnesota Minneapolis MN55455 USA

Nanog is a newly identified homeodomain gene that functions to sustain the pluripotency of embryonic stem cells. However, the molecular mechanism through which nanog regulates stem cell pluripotency remains unknown. Mouse nanog encodes a polypeptide of 305 residues with a divergent homeodomain similar to those in the NK-2.family. The rest of nanog contains no apparent homology to any known proteins characterized so far. It is hypothesized that nanog encodes a transcription factor that regulates stem cell pluripotency by switching on or off target genes. To test this hypothesis, we constructed fusion proteins between nanog and DNA binding domains of the yeast transcription factor Gal4 and tested the transactivation potentials of these constructs. Our data demonstrate that both regions N- and C- terminal to the homeodomain have transcription activities. Despite the fact that it contains no apparent transactivation motifs, the C-terminal domain is about 7 times as active as the N-terminal one. This unique

关键词： nanog pluripotency stem cells self renewal transactivation domain homeoprotein homeodomain

PTEN,a general negative regulator of cyclin D expression

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Cell Research 2007年第4期17卷 291-292页

作者： Eirong Diao~1 ye-guang {2. ~1state key laboratory of Biomembrane and Membrane biotechnology,department of biological sciences and biotechnology Tsing-hua Universiry,beijing {12.,china statekey{2.ofBiomembraneandMembranebiotechnology DepartmentofBiologicalSciencesandBiotechnologyTsing-huaUniversityBeijing100084China

The tumor-suppressor phosphatase with tensin homol-ogy(PTEN)is frequently mutated in many malignanciesand is one of the most well studied tumor suppressor genes[1,2..PTEN,a lipid and protein dual phosphatase,plays avital role in embryonic development,cell growth,apoptosisand cell *** well-known function of PTEN isphosphatidylinositol-3(PI)-phosphatase,which functionsas a negative regulator of the PIkinase(PI3K)*** well established that PTEN regulates the G1-S transitionby modulating the expression of cyclin D1 and *** passage of any cell through cell cycles is subtlymodulated by a series of proteins,among which the mainplayers in animal cells include cyclins,CDKs(cyclin-de-pendent kinases,positive regulators)and CDK inhibitors(negative regulators such as p2.and *** Dsare key regulators during the G1 phase and there are threetypes of cyclin Ds,D1,D2.and D3 in mammalian cells[3].Although the phenotypic analyses of single cyclin Dknockout mice revealed that each of the D type cyclinsis sufficient to drive normal development of the majority

关键词： PTEN,a general negative regulator of cyclin D expression

Amip inhibits mesoderm induction activity of Nodal in zebrafish

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Amip inhibits mesoderm induction activity of Nodal in zebraf...

中国细胞生物学学会第八届会员代表大会暨学术大会

作者： Lixia Zhang, Hu Zhou, ye-guang {2. and Anming meng department of biological sciences and biotechnology, The state key laboratory of Biomembrane and Membrane biotechnology, tsinghua university, beijing 100084,{12.

Nodal is a TGFβ-related factor and has been identified as a key endogenous inducerfor both mesoderm and endoderm during vertebrate embryogenesis. In zebrafish,concurrent deficiency of Sqt and Cyc, two Nodal-related factors, lead to absence ofmost mesodermal and endodermal tissues in embryos. Here we report a zebrafishgene amip that encodes a novel component of the Nodal signaling pathway inzebrafish. amip mainly expresses in the territories where Sqt and Cyc have inductiveactivities during midblastula and gastrulation period. The expression of amip isnegatively autoregulated but activated by Nodal signaling. Knocking-down of Amip

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Pairs of thiol-substituted 1,2.4-triazole-based isomeric covalent inhibitors with tunable reactivity and selectivity

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Chinese Chemical Letters 2024年第7期35卷 329-335页

作者： Shiqi Xu Zi ye Shuang Shang Fengge Wang Huan Zhang Lianguo chen Hao Lin chen chen Fang Hua Chong-Jing Zhang state key {2. of Bioactive Substance and Function of Natural Medicines Beijing Key Laboratory of Active Substance Discovery and Druggability EvaluationInstitute of Materia MedicaChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100050China state key {2. of Bioactive Substance and Function of Natural Medicines Beijing Key Laboratory of New Drug Mechanisms and Pharmacological Evaluation Study(BZ0150)Institute of Materia MedicaPeking Union Medical College and Chinese Academy of Medical SciencesBeijing 100050China The First Affiliated Hospital of Wenzhou Medical university Wenzhou 325000China

Covalent bioactive compounds are successfully used in clinic and attracted intense research efforts in the fundamental study as well as drug *** advantageous effects of covalent compounds compared with non-covalent ones are highly dependent on electrophilic ***,electrophilic warheads with tunable reactivity and selectivity are highly demanded in fields of medicinal chemistry and chemical ***,we report a novel electrophilic warhead,chloromethyl group activated by thiol-substituted 1,2.***,a pair of regioisomers could be simultaneously occurred in the step of alkylation during the synthesis of this unique *** is a rare example that the alkylation could simultaneously generate these two separable regioisomers of 1,2.4-triazole at the nitrogen or sulfur *** covalent-working mechanism of this new warhead is confirmed by various chemoproteomics experiments including target identification and binding site ***,the reactivity and selectivity of this new electrophilic warhead could be efficiently tuned by virtue of stereo ***,one pair of regioisomers(19S and 19X)induced distinct modes of cell *** 19S could induce apoptosis of colon cancer cells while 19X could induce both apoptosis and ***,this study provides pairs of novel electrophilic warheads that could be useful not only in supporting the design of covalent compounds for drug discovery but also in providing chemical probes for the fundamental biological study.

关键词： Electrophilic warhead Covalent inhibitor 1,2.4-Triazole Chemical proteomics GSTO1

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Transiently Expressed Short Hairpin RNA Targeting 12. kDa Protein of Tobacco Mosaic Virus Interferes with Virus Infection

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Acta Biochimica et Biophysica Sinica 2006年第1期38卷 22-28页

作者： ming-Min ZHAO~(1,2.,De-Rong AN~(1*),Jian ZHAO~2.guang-Hua HUANG~3,Zu-Hua HE~4,and Jiang-{2. chen~3 ~1 College of Plant Protection,Northwest Science and Technology university of Agriculture and Forestry,Yangling 712.00,china ~2.College of Agriculture,Yangtze university,Jingzhou 43402.,china ~3 state key laboratory of Molecular Biology,Institute of Biochemistry and Cell Biology,Shanghai Institutes for biological {12., Chinese Academy of {12.,Shanghai 2.0031,china ~4 state key laboratory of Plant Molecular Genetics,Institute of Plant Physiology and Ecology,Shanghai Institutes for biological {12., Chinese Academy of {12.,Shanghai 2.0032.china College of Plant Protection Northwest Science and Technology University of Agriculture and Forestry Yangling 712100 China

RNA-interference (RNAi) silences gene expression by'guiding mRNA degradation in asequence-specific *** interfering RNA (siRNA),an intermediate of the RNAi pathway,has beenshown to be very effective in inhibiting virus infection in mammalian cells and cultured plant ***,wereport that Agrobacterium tumefaciens-mediated transient expression of short hairpin RNA (shRNA) couldinhibit tobacco mosaic virus (TMV) RNA accumulation by targeting the gene encoding the replication-asso-ciated 12. kDa protein in intact plant *** results indicate that transiently expressed shRNA efficientlyinterfered with TMV *** interference observed is sequence-specific,and time-and *** expressed shRNA corresponding to the TMV 12. kDa protein gene did not inhibit cucumbermosaic virus (CMV),an unrelated *** order to interfere with TMV accumulation in tobaccoleaves,it is essential for the shRNA constructs to be infiltrated into the same leaves as TMV *** support the view that RNAi opens the door for novel therapeutic procedures against virus *** propose that a combination of the RNAi technique and Agrobacterium-mediated transient expressioncould be employed as a potent antiviral treatment in plants.

关键词： tobacco mosaic virus 12. kDa protein RNA interference short hairpin RNA

Fstl1 Is a BMP4 Signaling Antagonist in Controlling Mouse Lung Development

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Fstl1 Is a BMP4 Signaling Antagonist in Controlling Mouse Lu...

“细胞活动生命活力”——中国细胞生物学学会全体会员代表大会暨第十二次学术大会

作者： Yan Geng~(*+),Yingying Dong~(*+),ye-guang {2.~(*),and Wen Ning~(*‖**) +Model Animal Research Center,Nanjing university,Nanjing 2.0061,china state key laboratory of Biomembrane and Membrane biotechnology,School of Life sciences,tsinghua university,{12. 100084,china ‖College of Life sciences,Nankai university,Tianjin 300071,china.

Lung morphogenesis is a well-orchestrated,tightly regulated process through several molecular pathways including TGF/BMP *** of these signaling pathways leads to lung malformation. We herein investigated the role of Follistatin-like 1(Fstl1),a secreted follistatin-module containing glycoprotein,in lung *** of Fstl1 in mice led to postnatal lethality due to respiratory *** of the mutant phenotype showed that Fstl1 is essential for tracheal cartilage formation and alveolar *** of the Fstl1 gene resulted in malformed tracheal rings manifested as discontinued rings and reduced ring ***1 deficient mice displayed septal hypercellularity and end-expiratory atelectasis,which were associated with impaired differentiation of distal alveolar epithelial cells and insufficient production of mature surfactant ***,Fstl1 interacted directly with BMP4,negatively regulated BMP4/Smad 1/5/8 signaling,and inhibited BMP4-induced surfactant gene *** BMP signaling activity by Noggin rescued pulmonary atelectasis of Fstl1 deficient ***,we provide in vivo and in vitro evidence to demonstrate that Fstl1 modulates lung development and alveolar maturation,in part,through BMP4 signaling.

关键词： Fstll respiratory failure tracheal cartilage differentiation of alveolar epithelial cell BMP4

Termination of TGFβ superfamily signaling through SMAD dephosphorylation - A functional genomic view

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Termination of TGFβ superfamily signaling through SMAD deph...

中国遗传学会功能基因组学研讨会

作者： Xia Lin,ye-guang {2.,Anming meng , and Xin-Hua Feng (Michael E. DeBakey department of Surgery, department of Molecular & Cellular Biology, and Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030 state key laboratory of Biomembrane and Membrane biotechnology, and{12., tsinghua university, beijing 100084, china)

Members of the transforming growth factor-β(TGF-β) superfamily are secreted polypeptides that activate a broad range of cellular responses in metazoan organism. TGF-β and related factors inhibit the growth of most epithelial and hematopoietic cells and regulate the production of extracellular matrix by mesenchymal cells. These peptide growth factors are now known to act via autocrine, paracrine, and

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MicroRNA miR-2. Inhibits Erythropoiesis through Targeting Activin Type Ⅰ Receptor ALK4

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MicroRNA miR-24 Inhibits Erythropoiesis through Targeting Ac...

中国细胞生物学学会第九次会员代表大会暨青年学术大会

作者： Qiang Wang~1 Zheng Huang~2.Xue Hui-Ling~2.Xiu-Li Ju~3 Jing-Dong J.Han~2.ye-guang {2.~1 1 state key laboratory of Biomembrane and Membrane biotechnology,department of biological sciences and biotechnology,tsinghua {12.,beijing 100084,china 2.CAS key laboratory of Molecular Developmental Biology and Center for Molecular Systems Biology,Institute of Genetics and Developmental Biology,the Chinese Academy of sciences,beijing 100101,china 3 department of Pediatrics,Qilu Hospital of Shandong {12.,Jinan 2.0012.china

MicroRNAs have been suggested to modulate a variety of cellular *** we report that miR-2. regulates erythroid differentiation by influencing the expression of human activin type I receptor ALK4 (hALK4).Ectopic express... 详细信息

关键词： microRNA miR-2. activin ALK4 erythopoiesis