Imperial College London
Alternate

DrWeiCui

Faculty of Medicine, Department of Metabolism, Digestion and Reproduction

Senior Lecturer
 
 
 
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Contact

 

+44 (0)20 7594 2124wei.cui Website

 
 
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Location

 

1010Institute of Reproductive and Developmental BiologyHammersmith Campus

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Summary

 

Publications

Publication Type
Year
to

82 results found

Cui W, Yu J, 2016, Proliferation, survival and metabolism: the role of PI3K/AKT/mTOR signalling in pluripotency and cell fate determination, Development, Vol: 143, Pages: 3050-3060, ISSN: 0950-1991

Phosphatidylinositide 3 kinases (PI3Ks) and their downstream mediators AKT and mammaliantarget of rapamycin (mTOR) constitute the core components of the PI3K/AKT/mTORsignalling cascade, regulating cell proliferation, survival and metabolism. Although thesefunctions are well defined in the context of tumorigenesis, recent studies – in particular thoseusing pluripotent stem cells – have highlighted the importance of this pathway to developmentand cellular differentiation. Here we review the recent in vitro and in vivo evidence for the rolePI3K/Akt/mTOR signalling plays in the control of pluripotency and differentiation, with aparticular focus on the molecular mechanisms underlying these functions.

Journal article

Ovando-Roche P, Cui W, 2015, Identification of Factors in Regulating a Protein Ubiquitination by Immunoprecipitation: a Case Study of TRF2 on Human REST4 Ubiquitination., Bio-protocol, Vol: 5, ISSN: 2331-8325

Ubiquitination is the first step of the ubiquitin-proteasome pathway that regulates cells for their homeostatic functions and is an enzymatic, protein post-translational modification process in which ubiquitin is transferred to a target protein substrate by a set of three ubiquitin enzymes (Weissman et al., 2011; Bhattacharyya et al., 2014; Ristic et al., 2014). Given the importance of this process, it is plausible that ubiquitination is under strict control by many factors and that the regulatory machineries are protein-specific. An assay for the detection of a specific protein ubiquitination will enable us to examine whether a factor has a function to regulate the ubiquitination of this protein. Here we describe a protocol that detects the ubiquitination status of the human REST4 protein in cultured cells, a neural alternative splicing isoform of REST (RE-1 silencing transcription factor), that antagonizes the repressive function of REST on neural differentiation and neuron formation. Using this protocol, we show that the telomere binding protein TRF2 stabilizes the expression of the human REST4 by inhibiting its ubiquitination. This indicates that TRF2 plays a positive role in neural differentiation (Ovando-Roche et al., 2014). This protocol is also useful for the detection of ubiquitination of other proteins of interest.

Journal article

Yu JS, Ramasamy TS, Murphy N, Holt MK, Czapiewski R, Wei SK, Cui Wet al., 2015, PI3K/mTORC2 regulates TGF-β/Activin signalling by modulating Smad2/3 activity via linker phosphorylation, Nature Communications, Vol: 6, ISSN: 2041-1723

Crosstalk between the phosphatidylinositol 3-kinase (PI3K) and the transforming growth factor-β signalling pathways play an important role in regulating many cellular functions. However, the molecular mechanisms underpinning this crosstalk remain unclear. Here, we report that PI3K signalling antagonizes the Activin-induced definitive endoderm (DE) differentiation of human embryonic stem cells by attenuating the duration of Smad2/3 activation via the mechanistic target of rapamycin complex 2 (mTORC2). Activation of mTORC2 regulates the phosphorylation of the Smad2/3-T220/T179 linker residue independent of Akt, CDK and Erk activity. This phosphorylation primes receptor-activated Smad2/3 for recruitment of the E3 ubiquitin ligase Nedd4L, which in turn leads to their degradation. Inhibition of PI3K/mTORC2 reduces this phosphorylation and increases the duration of Smad2/3 activity, promoting a more robust mesendoderm and endoderm differentiation. These findings present a new and direct crosstalk mechanism between these two pathways in which mTORC2 functions as a novel and critical mediator.

Journal article

Noisa P, Raivio T, Cui W, 2015, Neural Progenitor Cells Derived from Human Embryonic Stem Cells as an Origin of Dopaminergic Neurons, Stem Cells International, Vol: 2015, ISSN: 1687-9678

Human embryonic stem cells (hESCs) are able to proliferate in vitro indefinitely without losing their ability to differentiate into multiple cell types upon exposure to appropriate signals. Particularly, the ability of hESCs to differentiate into neuronal subtypes is fundamental to develop cell-based therapies for several neurodegenerative disorders, such as Alzheimer’s disease, Huntington’s disease, and Parkinson’s disease. In this study, we differentiated hESCs to dopaminergic neurons via an intermediate stage, neural progenitor cells (NPCs). hESCs were induced to neural progenitor cells by Dorsomorphin, a small molecule that inhibits BMP signalling. The resulting neural progenitor cells exhibited neural bipolarity with high expression of neural progenitor genes and possessed multipotential differentiation ability. CBF1 and bFGF responsiveness of these hES-NP cells suggested their similarity to embryonic neural progenitor cells. A substantial number of dopaminergic neurons were derived from hES-NP cells upon supplementation of FGF8 and SHH, key dopaminergic neuron inducers. Importantly, multiple markers of midbrain neurons were detected, including NURR1, PITX3, and EN1, suggesting that hESC-derived dopaminergic neurons attained the midbrain identity. Altogether, this work underscored the generation of neural progenitor cells that retain the properties of embryonic neural progenitor cells. These cells will serve as an unlimited source for the derivation of dopaminergic neurons, which might be applicable for treating patients with Parkinson’s disease.

Journal article

Tan GC, Chan E, Molnar A, Sarkar R, Alexieva D, Isa IM, Robinson S, Zhang S, Ellis P, Langford CF, Guillot PV, Chandrashekran A, Fisk NM, Castellano L, Meister G, Winston RM, Cui W, Baulcombe D, Dibb NJet al., 2014, 5 ' isomiR variation is of functional and evolutionary importance, Nucleic Acids Research, Vol: 42, Pages: 9424-9435, ISSN: 1362-4962

We have sequenced miRNA libraries from human embryonic,neural and foetal mesenchymal stem cells.We report that the majority of miRNA genes encodemature isomers that vary in size by one ormore bases at the 3 and/or 5 end of the miRNA.Northern blotting for individual miRNAs showed thatthe proportions of isomiRs expressed by a singlemiRNA gene often differ between cell and tissuetypes. IsomiRs were readily co-immunoprecipitatedwith Argonaute proteins in vivo and were active inluciferase assays, indicating that they are functional.Bioinformatics analysis predicts substantial differencesin targeting between miRNAs with minor 5differences and in support of this we report that a 5isomiR-9–1 gained the ability to inhibit the expressionof DNMT3B and NCAM2 but lost the ability toinhibit CDH1 in vitro. This result was confirmed bythe use of isomiR-specific sponges. Our analysis ofthe miRGator database indicates that a small percentageof human miRNA genes express isomiRs asthe dominant transcript in certain cell types and analysisof miRBase shows that 5 isomiRs have replacedcanonical miRNAs many times during evolution. Thisstrongly indicates that isomiRs are of functional importanceand have contributed to the evolution ofmiRNA genes.INT

Journal article

Zhang S, Cui W, 2014, Sox2, a key factor in the regulation of pluripotency and neural differentiation., World Journal of Stem Cells, Vol: 6, Pages: 305-311, ISSN: 1948-0210

Sex determining region Y-box 2 (Sox2), a member of the SoxB1 transcription factor family, is an important transcriptional regulator in pluripotent stem cells (PSCs). Together with octamer-binding transcription factor 4 and Nanog, they co-operatively control gene expression in PSCs and maintain their pluripotency. Furthermore, Sox2 plays an essential role in somatic cell reprogramming, reversing the epigenetic configuration of differentiated cells back to a pluripotent embryonic state. In addition to its role in regulation of pluripotency, Sox2 is also a critical factor for directing the differentiation of PSCs to neural progenitors and for maintaining the properties of neural progenitor stem cells. Here, we review recent findings concerning the involvement of Sox2 in pluripotency, somatic cell reprogramming and neural differentiation as well as the molecular mechanisms underlying these roles.

Journal article

Ovando-Roche P, Yu JSL, Testori S, Ho C, Cui Wet al., 2014, TRF2-Mediated Stabilization of hREST4 Is Critical for the Differentiation and Maintenance of Neural Progenitors, Stem Cells, Vol: 32, Pages: 2111-2122, ISSN: 1549-4918

Telomere repeat binding factor 2 (TRF2) is a component of the shelterin complex that is knownto bind and protect telomeric DNA, yet the detection of TRF2 in extra-telomeric regions of chromosomessuggests other roles for TRF2 besides telomere protection. Here, we demonstrate thatTRF2 plays a critical role in antagonizing the repressive function of neuron-restrictive silencerfactor, also known as repressor element-1 silencing transcription factor (REST), during the neuraldifferentiation of human embryonic stem cells (hESCs) by enhancing the expression of a truncatedREST splice isoform we term human REST4 (hREST4) due to its similarity to rodent REST4.We show that TRF2 is specifically upregulated during hESC neural differentiation concordantlywith an increase in the expression of hREST4 and that both proteins are highly expressed inNPCs. Overexpression of TRF2 in hESCs increases hREST4 levels and induces their neural differentiation,whereas TRF2 knockdown in hESCs and NPCs reduces hREST4 expression, hinderingtheir ability to differentiate to the neural lineage. Concurrently, we show that TRF2 directlyinteracts with the C-terminal of hREST4 through its TRF2 core binding motif [F/Y]xL, protectinghREST4 from ubiquitin-mediated proteasomal degradation and consequently furthering neuralinduction. Thus, the TRF2-mediated counterbalance between hREST4 and REST is vital for boththe generation and maintenance of NPCs, suggesting an important role for TRF2 in both neurogenesisand function of the central nervous system.

Journal article

Ramasamy TS, Yu JSL, Selden C, Hodgson H, Cui Wet al., 2013, Application of Three-Dimensional Culture Conditions to Human Embryonic Stem Cell-Derived Definitive Endoderm Cells Enhances Hepatocyte Differentiation and Functionality, TISSUE ENGINEERING PART A, Vol: 19, Pages: 360-367, ISSN: 1937-3341

Journal article

Surmacz B, Noisa P, Risner-Janiczek JR, Hui K, Ungless M, Cui W, Li Met al., 2012, DLK1 Promotes Neurogenesis of Human and Mouse Pluripotent Stem Cell-Derived Neural Progenitors Via Modulating Notch and BMP Signalling, STEM CELL REVIEWS AND REPORTS, Vol: 8, Pages: 459-471, ISSN: 2629-3269

Journal article

Noisa P, Ramasamy TS, Lamont FR, Yu JSL, Sheldon MJ, Russell A, Jin X, Cui Wet al., 2012, Identification and Characterisation of the Early Differentiating Cells in Neural Differentiation of Human Embryonic Stem Cells, PLOS ONE, Vol: 7, ISSN: 1932-6203

Journal article

Noisa P, Urrutikoetxea-Uriguen A, Cui W, 2011, Generation of human embryonic stem cells carrying lineage specific reporters, Embryonic stem cell therapy for osteodegenerative diseases, Editors: zur Nieden, Publisher: Humana Press, Pages: 95-106

Book chapter

Ramasamy TS, Cui W, 2010, Inhibition of phosphatidylinositol-3-kinase signalling promotes Activin A induced definitive endoderm differentiation of human embryonic stem cells, DIFFERENTIATION, Vol: 80, Pages: S25-S25, ISSN: 0301-4681

Journal article

Olmer R, Haase A, Merkert S, Cui W, Palecek J, Ran C, Kirschning A, Scheper T, Glage S, Miller K, Curnow EC, Hayes ES, Martin Uet al., 2010, Long term expansion of undifferentiated human iPS and ES cells in suspension culture using a defined medium, STEM CELL RESEARCH, Vol: 5, Pages: 51-64, ISSN: 1873-5061

Journal article

Noisa P, Urrutikoetxea-Uriguen A, Li M, Cui Wet al., 2010, Generation of Human Embryonic Stem Cell Reporter Lines Expressing GFP Specifically in Neural Progenitors, STEM CELL REVIEWS AND REPORTS, Vol: 6, Pages: 438-449, ISSN: 2629-3269

Journal article

Narva E, Autio R, Rahkonen N, Kong L, Harrison N, Kitsberg D, Borghese L, Itskovitz-Eldor J, Rasool O, Dvorak P, Hovatta O, Otonkoski T, Tuuri T, Cui W, Brustle O, Baker D, Maltby E, Moore HD, Benvenisty N, Andrews PW, Yli-Harja O, Lahesmaa Ret al., 2010, High-resolution DNA analysis of human embryonic stem cell lines reveals culture-induced copy number changes and loss of heterozygosity, NATURE BIOTECHNOLOGY, Vol: 28, Pages: 371-U103, ISSN: 1087-0156

Journal article

Wu JQ, Habegger L, Noisa P, Szekely A, Qiu C, Hutchison S, Raha D, Egholm M, Lin H, Weissman S, Cui W, Gerstein M, Snyder Met al., 2010, Dynamic transcriptomes during neural differentiation of human embryonic stem cells revealed by short, long, and paired-end sequencing, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, Vol: 107, Pages: 5254-5259, ISSN: 0027-8424

Journal article

Szekely AM, Wu JQ, Habegger L, Noisa P, Qiu C, Hutchison S, Raha D, Egholm M, Lin H, Weissman SM, Cui W, Gerstein M, Snyder Met al., 2010, Dynamic Transcriptomes during Neural Differentiation of Human Embryonic Stem Cells Revealed by Short, Long, and Paired-End Sequencing, 62nd Annual Meeting of the American-Academy-of-Neurology, Publisher: LIPPINCOTT WILLIAMS & WILKINS, Pages: A4-A4, ISSN: 0028-3878

Conference paper

Olmer R, Haase A, Merkert S, Schwanke K, Cui W, Martin Uet al., 2009, Expansion of undifferentiated human iPS and human ES cells in suspension culture using a largely defined medium, Combined Meeting of the 17th European-Society-of-Gene-and-Cell-Therapy/16th German-Society-for-Gene-Therapy/4th German-Society-for-Stem-Cell-Research, Publisher: MARY ANN LIEBERT INC, Pages: 1394-1395, ISSN: 1043-0342

Conference paper

Lebkowski JS, Cui W, Hay DC, 2009, Direct Differentiation of Human Embryonic Stem Cells to Hepatocyte-like Cells Exhibiting Functional Activities (vol 9, pg 51, 2007), CLONING AND STEM CELLS, Vol: 11, Pages: 209-209, ISSN: 1536-2302

Journal article

Olmer R, Haase A, Merkert S, Schwanke K, Cui W, Martin Uet al., 2009, Human Oct3/4 Promoter Dependent Lentiviral Transgene Expression for Simplified Monitoring of Primate Embryonic Stem Cell Culture, 3rd Congress on Regenerative Biology and Medicine/3rd Congress of the German-Society-for-Stem-Cell-Research, Publisher: MARY ANN LIEBERT INC, Pages: 727-727, ISSN: 1937-3341

Conference paper

Pereira CF, Terranova R, Ryan NK, Santos J, Morris KJ, Cui W, Merkenschlager M, Fisher AGet al., 2008, Heterokaryon-based reprogramming of human B lymphocytes for pluripotency requires Oct4 but not Sox2, PLoS Genetics, Vol: 4, ISSN: 1553-7390

Differentiated cells can be reprogrammed through the formation of heterokaryons and hybrid cells when fused withembryonic stem (ES) cells. Here, we provide evidence that conversion of human B-lymphocytes towards a multipotent stateis initiated much more rapidly than previously thought, occurring in transient heterokaryons before nuclear fusion and celldivision. Interestingly, reprogramming of human lymphocytes by mouse ES cells elicits the expression of a human ESspecific gene profile, in which markers of human ES cells are expressed (hSSEA4, hFGF receptors and ligands), but markersthat are specific to mouse ES cells are not (e.g., Bmp4 and LIF receptor). Using genetically engineered mouse ES cells, wedemonstrate that successful reprogramming of human lymphocytes is independent of Sox2, a factor thought to be requiredfor induced pluripotent stem (iPS) cells. In contrast, there is a distinct requirement for Oct4 in the establishment but not themaintenance of the reprogrammed state. Experimental heterokaryons, therefore, offer a powerful approach to trace thecontribution of individual factors to the reprogramming of human somatic cells towards a multipotent state.

Journal article

Fletcher J, Cui W, Samuel K, Black JR, Hannoun Z, Currie IS, Terrace JD, Payne C, Filippi C, Newsome P, Forbes SJ, Ross JA, Iredale JP, Hay DCet al., 2008, The inhibitory role of stromal cell mesenchyme on human embryonic stem cell hepatocyte differentiation is overcome by Wnt3a treatment, CLONING AND STEM CELLS, Vol: 10, Pages: 331-339, ISSN: 1536-2302

Journal article

Zhao D, Hay D, Fletcher J, Hewitt Z, McLean D, Black J, Urruticoechea-Uriguen A, Elcombe C, Ross J, Wolf R, Cui Wet al., 2008, Control differentiation of embryonic stem cell to specific lineages, CELL RESEARCH, Vol: 18, ISSN: 1001-0602

Journal article

Rahman R, Forsyth NR, Cui W, 2008, Telomeric 3′-overhang length is associated with the size of telomeres, EXPERIMENTAL GERONTOLOGY, Vol: 43, Pages: 258-265, ISSN: 0531-5565

Journal article

Hay DC, Zhao D, Fletcher J, Hewitt ZA, McLean D, Urruticoechea-Uriguen A, Black JR, Elcombe C, Ross JA, Wolf R, Cui Wet al., 2008, Efficient differentiation of hepatocytes from human embryonic stem cells exhibiting markers recapitulating liver development in vivo, STEM CELLS, Vol: 26, Pages: 894-902, ISSN: 1066-5099

Journal article

Guillot PV, Cui W, 2008, Stem cells differentiation, Advances in Tissue Engineering, Pages: 83-93, ISBN: 9781848161825

Stem cells (both embryonic and somatic) have the capacity to self-renew and differentiate into specific lineage under permissive conditions. Although progress has been made on differentiation of pluripotent ES to a defined cell type, it is far from clear which are the signalling pathways controlling differentiation of a defined cell type and even less known about how to differentiate ES cells to be a functional cell type. Along with ES cells, foetal mesenchymal stem cells (MSC) are the only stem cells to be pluritpotent, expressing Oct-4 and Nanog, while adult MSC remain multipotent.

Book chapter

Guillot PV, Cui W, Fisk NM, Polak DJet al., 2007, Stem cell differentiation and expansion for clinical applications of tissue engineering, JOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Vol: 11, Pages: 935-944, ISSN: 1582-1838

Journal article

Hay DC, Zhao D, Ross A, Mandalam R, Lebkowski J, Cui Wet al., 2007, Direct differentiation of human embryonic stem cells to hepatocyte-like cells exhibiting functional activities, CLONING AND STEM CELLS, Vol: 9, Pages: 51-62, ISSN: 1536-2302

Journal article

Rahman R, Mo L, Cui W, 2006, Telomerase with mutated catalytic motifs has dominant negative effects on telomerase activity and inhibits cell growth, BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, Vol: 350, Pages: 796-802, ISSN: 0006-291X

Journal article

Gerrard L, Rodgers L, Cui W, 2005, Differentiation of human embryonic stem cells to neural lineages in adherent culture by blocking bone morphogenetic protein signaling, STEM CELLS, Vol: 23, Pages: 1234-1241, ISSN: 1066-5099

Journal article

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