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  1. Article ; Online: Clonal transcriptomics identifies mechanisms of chemoresistance and empowers rational design of combination therapies.

    Wild, Sophia A / Cannell, Ian G / Nicholls, Ashley / Kania, Katarzyna / Bressan, Dario / Hannon, Gregory J / Sawicka, Kirsty

    eLife

    2022  Volume 11

    Abstract: Tumour heterogeneity is thought to be a major barrier to successful cancer treatment due to the presence of drug resistant clonal lineages. However, identifying the characteristics of such lineages that underpin resistance to therapy has remained ... ...

    Abstract Tumour heterogeneity is thought to be a major barrier to successful cancer treatment due to the presence of drug resistant clonal lineages. However, identifying the characteristics of such lineages that underpin resistance to therapy has remained challenging. Here, we utilise clonal transcriptomics with WILD-seq;
    MeSH term(s) Humans ; Mice ; Animals ; Drug Resistance, Neoplasm/genetics ; Nuclear Proteins ; Transcriptome ; Asparagine ; Transcription Factors ; Triple Negative Breast Neoplasms/pathology ; Taxoids/pharmacology ; Taxoids/therapeutic use
    Chemical Substances Nuclear Proteins ; Asparagine (7006-34-0) ; Transcription Factors ; taxane (1605-68-1) ; Taxoids
    Language English
    Publishing date 2022-12-16
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2687154-3
    ISSN 2050-084X ; 2050-084X
    ISSN (online) 2050-084X
    ISSN 2050-084X
    DOI 10.7554/eLife.80981
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: FOXC2 promotes vasculogenic mimicry and resistance to anti-angiogenic therapy.

    Cannell, Ian G / Sawicka, Kirsty / Pearsall, Isabella / Wild, Sophia A / Deighton, Lauren / Pearsall, Sarah M / Lerda, Giulia / Joud, Fadwa / Khan, Showkhin / Bruna, Alejandra / Simpson, Kathryn L / Mulvey, Claire M / Nugent, Fiona / Qosaj, Fatime / Bressan, Dario / Dive, Caroline / Caldas, Carlos / Hannon, Gregory J

    Cell reports

    2023  Volume 42, Issue 8, Page(s) 112791

    Abstract: Vasculogenic mimicry (VM) describes the formation of pseudo blood vessels constructed of tumor cells that have acquired endothelial-like properties. VM channels endow the tumor with a tumor-derived vascular system that directly connects to host blood ... ...

    Abstract Vasculogenic mimicry (VM) describes the formation of pseudo blood vessels constructed of tumor cells that have acquired endothelial-like properties. VM channels endow the tumor with a tumor-derived vascular system that directly connects to host blood vessels, and their presence is generally associated with poor patient prognosis. Here we show that the transcription factor, Foxc2, promotes VM in diverse solid tumor types by driving ectopic expression of endothelial genes in tumor cells, a process that is stimulated by hypoxia. VM-proficient tumors are resistant to anti-angiogenic therapy, and suppression of Foxc2 augments response. This work establishes co-option of an embryonic endothelial transcription factor by tumor cells as a key mechanism driving VM proclivity and motivates the search for VM-inhibitory agents that could form the basis of combination therapies with anti-angiogenics.
    MeSH term(s) Humans ; Neovascularization, Pathologic/metabolism ; Cell Line, Tumor ; Immunotherapy
    Language English
    Publishing date 2023-07-26
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 2649101-1
    ISSN 2211-1247 ; 2211-1247
    ISSN (online) 2211-1247
    ISSN 2211-1247
    DOI 10.1016/j.celrep.2023.112791
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: lncRNA Spehd Regulates Hematopoietic Stem and Progenitor Cells and Is Required for Multilineage Differentiation.

    Delás, M Joaquina / Jackson, Benjamin T / Kovacevic, Tatjana / Vangelisti, Silvia / Munera Maravilla, Ester / Wild, Sophia A / Stork, Eva Maria / Erard, Nicolas / Knott, Simon R V / Hannon, Gregory J

    Cell reports

    2019  Volume 27, Issue 3, Page(s) 719–729.e6

    Abstract: Long non-coding RNAs (lncRNAs) show patterns of tissue- and cell type-specific expression that are very similar to those of protein coding genes and consequently have the potential to control stem and progenitor cell fate decisions along a ... ...

    Abstract Long non-coding RNAs (lncRNAs) show patterns of tissue- and cell type-specific expression that are very similar to those of protein coding genes and consequently have the potential to control stem and progenitor cell fate decisions along a differentiation trajectory. To understand the roles that lncRNAs may play in hematopoiesis, we selected a subset of mouse lncRNAs with potentially relevant expression patterns and refined our candidate list using evidence of conserved expression in human blood lineages. For each candidate, we assessed its possible role in hematopoietic differentiation in vivo using competitive transplantation. Our studies identified two lncRNAs that were required for hematopoiesis. One of these, Spehd, showed defective multilineage differentiation, and its silencing yielded common myeloid progenitors that are deficient in their oxidative phosphorylation pathway. This effort not only suggests that lncRNAs can contribute to differentiation decisions during hematopoiesis but also provides a path toward the identification of functional lncRNAs in other differentiation hierarchies.
    MeSH term(s) Animals ; Bone Marrow Transplantation ; Cell Differentiation ; Cell Line, Tumor ; Cell Lineage ; Cyclin-Dependent Kinase 6/genetics ; Cyclin-Dependent Kinase 6/metabolism ; Female ; GATA2 Transcription Factor/genetics ; GATA2 Transcription Factor/metabolism ; Hematopoiesis ; Hematopoietic Stem Cells/cytology ; Hematopoietic Stem Cells/metabolism ; Mice ; Mice, Inbred C57BL ; Oxidative Phosphorylation ; Proto-Oncogene Proteins/antagonists & inhibitors ; Proto-Oncogene Proteins/genetics ; Proto-Oncogene Proteins/metabolism ; RNA Interference ; RNA, Long Noncoding/antagonists & inhibitors ; RNA, Long Noncoding/genetics ; RNA, Long Noncoding/metabolism ; RNA, Small Interfering/metabolism ; Regeneration ; Trans-Activators/antagonists & inhibitors ; Trans-Activators/genetics ; Trans-Activators/metabolism
    Chemical Substances Ebf1 protein, mouse ; GATA2 Transcription Factor ; Gata2 protein, mouse ; Proto-Oncogene Proteins ; RNA, Long Noncoding ; RNA, Small Interfering ; Trans-Activators ; proto-oncogene protein Spi-1 ; Cdk6 protein, mouse (EC 2.7.11.22) ; Cyclin-Dependent Kinase 6 (EC 2.7.11.22)
    Language English
    Publishing date 2019-04-16
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2649101-1
    ISSN 2211-1247 ; 2211-1247
    ISSN (online) 2211-1247
    ISSN 2211-1247
    DOI 10.1016/j.celrep.2019.03.080
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: lncRNA requirements for mouse acute myeloid leukemia and normal differentiation.

    Delás, M Joaquina / Sabin, Leah R / Dolzhenko, Egor / Knott, Simon Rv / Munera Maravilla, Ester / Jackson, Benjamin T / Wild, Sophia A / Kovacevic, Tatjana / Stork, Eva Maria / Zhou, Meng / Erard, Nicolas / Lee, Emily / Kelley, David R / Roth, Mareike / Barbosa, Inês Am / Zuber, Johannes / Rinn, John L / Smith, Andrew D / Hannon, Gregory J

    eLife

    2017  Volume 6

    Abstract: A substantial fraction of the genome is transcribed in a cell-type-specific manner, producing long non-coding RNAs (lncRNAs), rather than protein-coding transcripts. Here, we systematically characterize transcriptional dynamics during hematopoiesis and ... ...

    Abstract A substantial fraction of the genome is transcribed in a cell-type-specific manner, producing long non-coding RNAs (lncRNAs), rather than protein-coding transcripts. Here, we systematically characterize transcriptional dynamics during hematopoiesis and in hematological malignancies. Our analysis of annotated and de novo assembled lncRNAs showed many are regulated during differentiation and mis-regulated in disease. We assessed lncRNA function via an in vivo RNAi screen in a model of acute myeloid leukemia. This identified several lncRNAs essential for leukemia maintenance, and found that a number act by promoting leukemia stem cell signatures. Leukemia blasts show a myeloid differentiation phenotype when these lncRNAs were depleted, and our data indicates that this effect is mediated via effects on the MYC oncogene. Bone marrow reconstitutions showed that a lncRNA expressed across all progenitors was required for the myeloid lineage, whereas the other leukemia-induced lncRNAs were dispensable in the normal setting.
    MeSH term(s) Animals ; Cell Differentiation ; Disease Models, Animal ; Gene Expression Profiling ; Gene Expression Regulation ; Hematopoiesis ; Leukemia, Myeloid, Acute/pathology ; Mice ; RNA, Long Noncoding/genetics ; RNA, Long Noncoding/metabolism
    Chemical Substances RNA, Long Noncoding
    Language English
    Publishing date 2017-09-06
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2687154-3
    ISSN 2050-084X ; 2050-084X
    ISSN (online) 2050-084X
    ISSN 2050-084X
    DOI 10.7554/eLife.25607
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

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