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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 {2. key laboratory of biomembrane and membrane biotechnology, School of Life sciences, tsinghua university, beijing 100084, China 1. The state key {2. of {2. 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, {12. 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. ~1{2. key laboratory of biomembrane and membrane biotechnology,department of biological sciences and biotechnology Tsing-hua Universiry,beijing 100084,China statekey{2.of{2.andmembranebiotechnology 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 An{2. meng department of biological sciences and biotechnology, The state key laboratory of biomembrane and membrane biotechnology,{12., beijing 100084, China

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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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 {2.,Nanjing 2.0061,China state key laboratory of biomembrane and membrane biotechnology,School of Life sciences,tsinghua {2.,beijing 100084,China ‖College of Life sciences,Nankai {2.,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.,An{2. 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 {12. biotechnology, and department of biological sciences and biotechnology, 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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小鼠海马锥体细胞树突棘形态的电镜三维重建

生物物理学报 2003年第1期19卷 18-22页

作者：杨光龚锴蒋五玲公衍道张秀芳赵南明清华大学生物科学与技术系

大多数神经元的复杂三维结构是很难直接观察的。激光扫描共聚焦显微镜技术结合染料标记技术可以重建神经元的三维形态,但精细结构的识别需要电子显微镜。利用透射电子显微镜技术,可以得到连续超薄组织切片的高分辨率图像,结合计算机支... 详细信息

大多数神经元的复杂三维结构是很难直接观察的。激光扫描共聚焦显微镜技术结合染料标记技术可以重建神经元的三维形态,但精细结构的识别需要电子显微镜。利用透射电子显微镜技术,可以得到连续超薄组织切片的高分辨率图像,结合计算机支持的三维重建技术就可进一步获得神经细胞精细结构的三维信息。通过电镜三维重建技术对未成熟和成熟小鼠海马锥体细胞树突棘的形态进行了观察和分析,并对其关键步骤的操作技巧进行了重点说明。实验结果为进一步利用成像技术研究树突棘的结构、功能和可塑性提供了重要信息。

关键词：透射电子显微镜连续超薄切片三维重建树突棘

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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 {2. key laboratory of biomembrane and membrane biotechnology,department of biological sciences and biotechnology,tsinghua university,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 university,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

Genome-wide Analysis of Smad Targets Reveals the Role of BMP Signaling in Embryonic Stem Cell Fate Determination

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Genome-wide Analysis of Smad Targets Reveals the Role of BMP...

第十一次中国生物物理学术大会暨第九届全国会员代表大会

作者： Teng Fei 1# ,Kai Xia 2. ,Zhang chen 2.,Hua chen 1 ,Zhongwei Li 1 ,Jianping Zhang 1 ,Bing Zhou 2.,Huasheng Xiao 3 ,Jing-Dong J.Han 2. ,{2.-{2. chen 1* 1The state key laboratory of biomembrane and membrane biotechnology, department of biological sciences and biotechnology,{12. university,beijing 100084,China 2.AS 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 3National Engineering Center for Biochip at Shanghai,Zhangjiang Hi-Tech Park, Shanghai,2.12.3,China

＜正＞Embryonic stem（ES）cells are under precise control of both intrinsic self-renewal gene regulatory network and extrinsic growth factor-triggered signaling *** external

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