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Childhood cerebellar tumours mirror conserved fetal transcriptional programs.
Vladoiu, Maria C; El-Hamamy, Ibrahim; Donovan, Laura K; Farooq, Hamza; Holgado, Borja L; Sundaravadanam, Yogi; Ramaswamy, Vijay; Hendrikse, Liam D; Kumar, Sachin; Mack, Stephen C; Lee, John J Y; Fong, Vernon; Juraschka, Kyle; Przelicki, David; Michealraj, Antony; Skowron, Patryk; Luu, Betty; Suzuki, Hiromichi; Morrissy, A Sorana; Cavalli, Florence M G; Garzia, Livia; Daniels, Craig; Wu, Xiaochong; Qazi, Maleeha A; Singh, Sheila K; Chan, Jennifer A; Marra, Marco A; Malkin, David; Dirks, Peter; Heisler, Lawrence; Pugh, Trevor; Ng, Karen; Notta, Faiyaz; Thompson, Eric M; Kleinman, Claudia L; Joyner, Alexandra L; Jabado, Nada; Stein, Lincoln; Taylor, Michael D.
Afiliação
  • Vladoiu MC; Developmental & Stem Cell Biology Program, The Hospital for Sick Children, Toronto, Ontario, Canada.
  • El-Hamamy I; The Arthur and Sonia Labatt Brain Tumor Research Centre, The Hospital for Sick Children, Toronto, Ontario, Canada.
  • Donovan LK; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
  • Farooq H; Computational Biology Program, Ontario Institute for Cancer Research, Toronto, Ontario, Canada.
  • Holgado BL; Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.
  • Sundaravadanam Y; Developmental & Stem Cell Biology Program, The Hospital for Sick Children, Toronto, Ontario, Canada.
  • Ramaswamy V; The Arthur and Sonia Labatt Brain Tumor Research Centre, The Hospital for Sick Children, Toronto, Ontario, Canada.
  • Hendrikse LD; Developmental & Stem Cell Biology Program, The Hospital for Sick Children, Toronto, Ontario, Canada.
  • Kumar S; The Arthur and Sonia Labatt Brain Tumor Research Centre, The Hospital for Sick Children, Toronto, Ontario, Canada.
  • Mack SC; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
  • Lee JJY; Developmental & Stem Cell Biology Program, The Hospital for Sick Children, Toronto, Ontario, Canada.
  • Fong V; The Arthur and Sonia Labatt Brain Tumor Research Centre, The Hospital for Sick Children, Toronto, Ontario, Canada.
  • Juraschka K; Computational Biology Program, Ontario Institute for Cancer Research, Toronto, Ontario, Canada.
  • Przelicki D; Developmental & Stem Cell Biology Program, The Hospital for Sick Children, Toronto, Ontario, Canada.
  • Michealraj A; The Arthur and Sonia Labatt Brain Tumor Research Centre, The Hospital for Sick Children, Toronto, Ontario, Canada.
  • Skowron P; Division of Haematology/Oncology, Department of Pediatrics, The Hospital for Sick Children, Toronto, Ontario, Canada.
  • Luu B; Developmental & Stem Cell Biology Program, The Hospital for Sick Children, Toronto, Ontario, Canada.
  • Suzuki H; The Arthur and Sonia Labatt Brain Tumor Research Centre, The Hospital for Sick Children, Toronto, Ontario, Canada.
  • Morrissy AS; Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.
  • Cavalli FMG; Developmental & Stem Cell Biology Program, The Hospital for Sick Children, Toronto, Ontario, Canada.
  • Garzia L; The Arthur and Sonia Labatt Brain Tumor Research Centre, The Hospital for Sick Children, Toronto, Ontario, Canada.
  • Daniels C; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
  • Wu X; Brain Tumor Program, Children's Cancer Center and Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.
  • Qazi MA; Developmental & Stem Cell Biology Program, The Hospital for Sick Children, Toronto, Ontario, Canada.
  • Singh SK; The Arthur and Sonia Labatt Brain Tumor Research Centre, The Hospital for Sick Children, Toronto, Ontario, Canada.
  • Chan JA; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
  • Marra MA; Developmental & Stem Cell Biology Program, The Hospital for Sick Children, Toronto, Ontario, Canada.
  • Malkin D; The Arthur and Sonia Labatt Brain Tumor Research Centre, The Hospital for Sick Children, Toronto, Ontario, Canada.
  • Dirks P; Developmental & Stem Cell Biology Program, The Hospital for Sick Children, Toronto, Ontario, Canada.
  • Heisler L; The Arthur and Sonia Labatt Brain Tumor Research Centre, The Hospital for Sick Children, Toronto, Ontario, Canada.
  • Pugh T; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
  • Ng K; Developmental & Stem Cell Biology Program, The Hospital for Sick Children, Toronto, Ontario, Canada.
  • Notta F; The Arthur and Sonia Labatt Brain Tumor Research Centre, The Hospital for Sick Children, Toronto, Ontario, Canada.
  • Thompson EM; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
  • Kleinman CL; Developmental & Stem Cell Biology Program, The Hospital for Sick Children, Toronto, Ontario, Canada.
  • Joyner AL; The Arthur and Sonia Labatt Brain Tumor Research Centre, The Hospital for Sick Children, Toronto, Ontario, Canada.
  • Jabado N; Developmental & Stem Cell Biology Program, The Hospital for Sick Children, Toronto, Ontario, Canada.
  • Stein L; The Arthur and Sonia Labatt Brain Tumor Research Centre, The Hospital for Sick Children, Toronto, Ontario, Canada.
  • Taylor MD; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
Nature ; 572(7767): 67-73, 2019 08.
Article em En | MEDLINE | ID: mdl-31043743
ABSTRACT
Study of the origin and development of cerebellar tumours has been hampered by the complexity and heterogeneity of cerebellar cells that change over the course of development. Here we use single-cell transcriptomics to study more than 60,000 cells from the developing mouse cerebellum and show that different molecular subgroups of childhood cerebellar tumours mirror the transcription of cells from distinct, temporally restricted cerebellar lineages. The Sonic Hedgehog medulloblastoma subgroup transcriptionally mirrors the granule cell hierarchy as expected, while group 3 medulloblastoma resembles Nestin+ stem cells, group 4 medulloblastoma resembles unipolar brush cells, and PFA/PFB ependymoma and cerebellar pilocytic astrocytoma resemble the prenatal gliogenic progenitor cells. Furthermore, single-cell transcriptomics of human childhood cerebellar tumours demonstrates that many bulk tumours contain a mixed population of cells with divergent differentiation. Our data highlight cerebellar tumours as a disorder of early brain development and provide a proximate explanation for the peak incidence of cerebellar tumours in early childhood.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Transcrição Gênica / Regulação Neoplásica da Expressão Gênica / Neoplasias Cerebelares / Regulação da Expressão Gênica no Desenvolvimento / Evolução Molecular / Feto Idioma: En Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Canadá
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Transcrição Gênica / Regulação Neoplásica da Expressão Gênica / Neoplasias Cerebelares / Regulação da Expressão Gênica no Desenvolvimento / Evolução Molecular / Feto Idioma: En Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Canadá