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  1. Article ; Online: The Glioma Stem Cell Model in the Era of Single-Cell Genomics.

    Suvà, Mario L / Tirosh, Itay

    Cancer cell

    2020  Volume 37, Issue 5, Page(s) 630–636

    Abstract: Glioma stem cells (GSCs) are thought to underlie glioma initiation, evolution, and resistance to existing therapies. Although functional evidence for GSCs is abundant, tumor heterogeneity and intrinsic limitations in GSC assays have represented barriers ... ...

    Abstract Glioma stem cells (GSCs) are thought to underlie glioma initiation, evolution, and resistance to existing therapies. Although functional evidence for GSCs is abundant, tumor heterogeneity and intrinsic limitations in GSC assays have represented barriers for the field. In this perspective, we revisit the GSC model in light of recent single-cell expression profiling studies. We highlight how classes of glioma differ in their cellular architecture and relate the observed cellular states to established GSC markers. We additionally propose a set of single-cell informed definitions as a framework for our understanding of the cellular architecture of gliomas and a potential therapeutic outlook.
    MeSH term(s) Animals ; Brain Neoplasms/genetics ; Brain Neoplasms/pathology ; Brain Neoplasms/therapy ; Genomics/methods ; Glioma/genetics ; Glioma/pathology ; Glioma/therapy ; Humans ; Neoplastic Stem Cells/metabolism ; Neoplastic Stem Cells/pathology ; Single-Cell Analysis/methods
    Language English
    Publishing date 2020-09-05
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2078448-X
    ISSN 1878-3686 ; 1535-6108
    ISSN (online) 1878-3686
    ISSN 1535-6108
    DOI 10.1016/j.ccell.2020.04.001
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  2. Article ; Online: Tackling the Many Facets of Glioblastoma Heterogeneity.

    Tirosh, Itay / Suvà, Mario L

    Cell stem cell

    2020  Volume 26, Issue 3, Page(s) 303–304

    Abstract: Glioblastoma is an incurable brain tumor notorious for its heterogeneity. Recent studies in Cell (Jacob et al., 2020) and Cell Stem Cell (Bhaduri et al., 2020) leverage novel glioblastoma organoid models and single-cell RNA-sequencing technologies to ... ...

    Abstract Glioblastoma is an incurable brain tumor notorious for its heterogeneity. Recent studies in Cell (Jacob et al., 2020) and Cell Stem Cell (Bhaduri et al., 2020) leverage novel glioblastoma organoid models and single-cell RNA-sequencing technologies to tackle glioblastoma's heterogeneous nature, providing new tools and insights into tumor biology.
    MeSH term(s) Biological Specimen Banks ; Brain Neoplasms ; Glioblastoma ; Humans ; Organoids ; Sequence Analysis, RNA
    Language English
    Publishing date 2020-04-22
    Publishing country United States
    Document type Journal Article ; Comment
    ZDB-ID 2375354-7
    ISSN 1875-9777 ; 1934-5909
    ISSN (online) 1875-9777
    ISSN 1934-5909
    DOI 10.1016/j.stem.2020.02.005
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  3. Article ; Online: Elucidating the diversity of malignant mesenchymal states in glioblastoma by integrative analysis.

    Chanoch-Myers, Rony / Wider, Adi / Suva, Mario L / Tirosh, Itay

    Genome medicine

    2022  Volume 14, Issue 1, Page(s) 106

    Abstract: Background: Multiple glioblastoma studies have described a mesenchymal (MES) state, with each study defining the MES program by distinct sets of genes and highlighting distinct functional associations, including both immune activation and suppression. ... ...

    Abstract Background: Multiple glioblastoma studies have described a mesenchymal (MES) state, with each study defining the MES program by distinct sets of genes and highlighting distinct functional associations, including both immune activation and suppression. These variable descriptions complicate our understanding of the MES state and its implications. Here, we hypothesize that there is a range of glioma MES states, possibly reflecting distinct prior states in which a MES program can be induced, and/or distinct mechanisms that induce the MES states in those cells.
    Methods: We integrated multiple published single-cell and bulk RNA sequencing datasets and MES signatures to define a core MES program that recurs across studies, as well as multiple function-specific MES signatures that vary across MES cells. We then examined the co-occurrence of these signatures and their associations with genetic and microenvironmental features.
    Results: Based on co-occurrence of MES signatures, we found three main variants of MES states: hypoxia-related (MES-Hyp), astrocyte-related (MES-Ast), and an intermediate state. Notably, the MES states are differentially associated with genetic and microenvironmental features. MES-Hyp is preferentially associated with NF1 deletion, overall macrophage abundance, a high macrophage/microglia ratio, and M2-related macrophages, consistent with previous studies that associated MES with immune suppression. In contrast, MES-Ast is associated with T cell abundance and cytotoxicity, consistent with immune activation through expression of MHC-I/II.
    Conclusions: Diverse MES states occur in glioblastoma. These states share a subset of core genes but differ primarily in their association with hypoxia vs. astrocytic expression programs, and with immune suppression vs. activation, respectively.
    MeSH term(s) Astrocytes/pathology ; Glioblastoma/genetics ; Glioblastoma/pathology ; Glioma/pathology ; Humans ; Hypoxia/pathology ; Neoplasm Recurrence, Local/pathology
    Language English
    Publishing date 2022-09-19
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2484394-5
    ISSN 1756-994X ; 1756-994X
    ISSN (online) 1756-994X
    ISSN 1756-994X
    DOI 10.1186/s13073-022-01109-8
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  4. Article ; Online: Correction: Elucidating the diversity of malignant mesenchymal states in glioblastoma by integrative analysis.

    Chanoch-Myers, Rony / Wider, Adi / Suva, Mario L / Tirosh, Itay

    Genome medicine

    2022  Volume 14, Issue 1, Page(s) 117

    Language English
    Publishing date 2022-10-12
    Publishing country England
    Document type Published Erratum
    ZDB-ID 2484394-5
    ISSN 1756-994X ; 1756-994X
    ISSN (online) 1756-994X
    ISSN 1756-994X
    DOI 10.1186/s13073-022-01122-x
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  5. Article ; Online: Ewing's Sarcoma.

    Riggi, Nicolò / Suvà, Mario L / Stamenkovic, Ivan

    The New England journal of medicine

    2021  Volume 384, Issue 2, Page(s) 154–164

    MeSH term(s) Antineoplastic Agents/therapeutic use ; Bone Neoplasms/genetics ; Bone Neoplasms/therapy ; Combined Modality Therapy ; DNA Methylation ; DNA, Neoplasm/metabolism ; Gene Expression Regulation ; Humans ; Mutation ; Oncogene Proteins, Fusion/metabolism ; Polymorphism, Genetic ; Prognosis ; Proto-Oncogene Protein c-fli-1/metabolism ; RNA-Binding Protein EWS/metabolism ; Sarcoma, Ewing/genetics ; Sarcoma, Ewing/therapy ; Suppression, Genetic ; Translocation, Genetic
    Chemical Substances Antineoplastic Agents ; DNA, Neoplasm ; EWS-FLI fusion protein ; Oncogene Proteins, Fusion ; Proto-Oncogene Protein c-fli-1 ; RNA-Binding Protein EWS
    Language English
    Publishing date 2021-01-26
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 207154-x
    ISSN 1533-4406 ; 0028-4793
    ISSN (online) 1533-4406
    ISSN 0028-4793
    DOI 10.1056/NEJMra2028910
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  6. Article ; Online: Ewing's Sarcoma. Reply.

    Riggi, Nicolò / Suvà, Mario L / Stamenkovic, Ivan

    The New England journal of medicine

    2021  Volume 384, Issue 15, Page(s) 1477–1478

    MeSH term(s) Bone Neoplasms ; Humans ; Sarcoma, Ewing/therapy ; Tumor Cells, Cultured
    Language English
    Publishing date 2021-04-14
    Publishing country United States
    Document type Letter ; Comment
    ZDB-ID 207154-x
    ISSN 1533-4406 ; 0028-4793
    ISSN (online) 1533-4406
    ISSN 0028-4793
    DOI 10.1056/NEJMc2102423
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  7. Article ; Online: Single-Cell RNA Sequencing in Cancer: Lessons Learned and Emerging Challenges.

    Suvà, Mario L / Tirosh, Itay

    Molecular cell

    2019  Volume 75, Issue 1, Page(s) 7–12

    Abstract: Bulk genomic analyses and expression profiling of clinical specimens have shaped much of our understanding of cancer in patients. However, human tumors are intricate ecosystems composed of diverse cells, including malignant, immune, and stromal subsets, ... ...

    Abstract Bulk genomic analyses and expression profiling of clinical specimens have shaped much of our understanding of cancer in patients. However, human tumors are intricate ecosystems composed of diverse cells, including malignant, immune, and stromal subsets, whose precise characterization is masked by bulk genomic methods. Single-cell genomic techniques have emerged as powerful approaches to dissect human tumors at the resolution of individual cells, providing a compelling approach to deciphering cancer biology. Here, we discuss some of the common themes emerging from initial studies of single-cell RNA sequencing in cancer and then highlight challenges in cancer biology for which emerging single-cell genomics methods may provide a compelling approach.
    MeSH term(s) Antineoplastic Agents/therapeutic use ; Cell Communication ; Cell Line, Tumor ; Cell Lineage ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; High-Throughput Nucleotide Sequencing/methods ; Humans ; Neoplasms/drug therapy ; Neoplasms/genetics ; Neoplasms/metabolism ; Neoplasms/pathology ; Neoplastic Cells, Circulating/metabolism ; Neoplastic Cells, Circulating/pathology ; RNA, Neoplasm/genetics ; RNA, Neoplasm/metabolism ; Single-Cell Analysis/methods
    Chemical Substances Antineoplastic Agents ; RNA, Neoplasm
    Language English
    Publishing date 2019-07-12
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 1415236-8
    ISSN 1097-4164 ; 1097-2765
    ISSN (online) 1097-4164
    ISSN 1097-2765
    DOI 10.1016/j.molcel.2019.05.003
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  8. Article: Single-Cell RNA Sequencing in Cancer: Lessons Learned and Emerging Challenges

    Suvà, Mario L / Tirosh, Itay

    Molecular cell. 2019 July 11, v. 75, no. 1

    2019  

    Abstract: Bulk genomic analyses and expression profiling of clinical specimens have shaped much of our understanding of cancer in patients. However, human tumors are intricate ecosystems composed of diverse cells, including malignant, immune, and stromal subsets, ... ...

    Abstract Bulk genomic analyses and expression profiling of clinical specimens have shaped much of our understanding of cancer in patients. However, human tumors are intricate ecosystems composed of diverse cells, including malignant, immune, and stromal subsets, whose precise characterization is masked by bulk genomic methods. Single-cell genomic techniques have emerged as powerful approaches to dissect human tumors at the resolution of individual cells, providing a compelling approach to deciphering cancer biology. Here, we discuss some of the common themes emerging from initial studies of single-cell RNA sequencing in cancer and then highlight challenges in cancer biology for which emerging single-cell genomics methods may provide a compelling approach.
    Keywords ecosystems ; genomics ; humans ; neoplasms ; patients ; sequence analysis
    Language English
    Dates of publication 2019-0711
    Size p. 7-12.
    Publishing place Elsevier Inc.
    Document type Article
    ZDB-ID 1415236-8
    ISSN 1097-4164 ; 1097-2765
    ISSN (online) 1097-4164
    ISSN 1097-2765
    DOI 10.1016/j.molcel.2019.05.003
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  9. Article ; Online: Decoding Cancer Biology One Cell at a Time.

    Gonzalez Castro, L Nicolas / Tirosh, Itay / Suvà, Mario L

    Cancer discovery

    2020  Volume 11, Issue 4, Page(s) 960–970

    Abstract: Human tumors are composed of diverse malignant and nonmalignant cells, generating a complex ecosystem that governs tumor biology and response to treatments. Recent technological advances have enabled the characterization of tumors at single-cell ... ...

    Abstract Human tumors are composed of diverse malignant and nonmalignant cells, generating a complex ecosystem that governs tumor biology and response to treatments. Recent technological advances have enabled the characterization of tumors at single-cell resolution, providing a compelling strategy to dissect their intricate biology. Here we describe recent developments in single-cell expression profiling and the studies applying them in clinical settings. We highlight some of the powerful insights gleaned from these studies for tumor classification, stem cell programs, tumor microenvironment, metastasis, and response to targeted and immune therapies. SIGNIFICANCE: Intratumor heterogeneity (ITH) has been a major barrier to our understanding of cancer. Single-cell genomics is leading a revolution in our ability to systematically dissect ITH. In this review, we focus on single-cell expression profiling and lessons learned in key aspects of human tumor biology.
    MeSH term(s) Humans ; Neoplasms/pathology ; Single-Cell Analysis ; Tumor Microenvironment
    Language English
    Publishing date 2020-07-28
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2625242-9
    ISSN 2159-8290 ; 2159-8274
    ISSN (online) 2159-8290
    ISSN 2159-8274
    DOI 10.1158/2159-8290.CD-20-1376
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  10. Article ; Online: Dissecting human gliomas by single-cell RNA sequencing.

    Tirosh, Itay / Suvà, Mario L

    Neuro-oncology

    2017  Volume 20, Issue 1, Page(s) 37–43

    Abstract: Diffuse gliomas are the most common human primary brain tumors and remain incurable. They are complex entities in which diverse genetic and nongenetic effects determine tumor biology and clinical course. Our current understanding of gliomas in patients ... ...

    Abstract Diffuse gliomas are the most common human primary brain tumors and remain incurable. They are complex entities in which diverse genetic and nongenetic effects determine tumor biology and clinical course. Our current understanding of gliomas in patients is primarily based on genomic and transcriptomic methods that have profiled them as bulk, providing critical information yet masking the diversity of cells within each tumor. Recent advances in single-cell DNA and RNA profiling have paved the way to studying tumors at cellular resolution. Here, we review initial studies deploying single-cell analysis in clinical glioma samples, with a focus on RNA expression profiling. We highlight how these studies provide new insights into glioma biology, tumor heterogeneity, cancer cell lineages, cancer stem cell programs, the tumor microenvironment, and glioma classification.
    MeSH term(s) Brain Neoplasms/genetics ; Brain Neoplasms/pathology ; Gene Expression Regulation, Neoplastic/genetics ; Glioma/genetics ; Glioma/pathology ; Humans ; Neoplastic Stem Cells/pathology ; Sequence Analysis, RNA/methods ; Tumor Microenvironment/genetics
    Language English
    Publishing date 2017-10-20
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 2028601-6
    ISSN 1523-5866 ; 1522-8517
    ISSN (online) 1523-5866
    ISSN 1522-8517
    DOI 10.1093/neuonc/nox126
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