Fiona J. Coutinho

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Functional heterogeneity within tumors presents a significant therapeutic challenge. Here we show that quiescent, therapy-resistant Sox2(+) cells propagate sonic hedgehog subgroup medulloblastoma by a mechanism that mirrors a neurogenic program. Rare Sox2(+) cells produce rapidly cycling doublecortin(+) progenitors that, together with their postmitotic(More)
Glioblastoma growth is driven by cancer cells that have stem cell properties, but molecular determinants of their tumorigenic behavior are poorly defined. In cancer, altered activity of the epigenetic modifiers Polycomb and Trithorax complexes may contribute to the neoplastic phenotype. Here, we provide the first mechanistic insights into the role of the(More)
Mutations in the histone 3 variant H3.3 have been identified in one-third of pediatric glioblastomas (GBMs), but not in adult tumors. Here we show that H3.3 is a dynamic determinant of functional properties in adult GBM. H3.3 is repressed by mixed lineage leukemia 5 (MLL5) in self-renewing GBM cells. MLL5 is a global epigenetic repressor that orchestrates(More)
Glioblastomas exhibit a hierarchical cellular organization, suggesting that they are driven by neoplastic stem cells that retain partial yet abnormal differentiation potential. Here, we show that a large subset of patient-derived glioblastoma stem cells (GSCs) express high levels of Achaete-scute homolog 1 (ASCL1), a proneural transcription factor involved(More)
Human glioblastomas harbour a subpopulation of glioblastoma stem cells that drive tumorigenesis. However, the origin of intratumoural functional heterogeneity between glioblastoma cells remains poorly understood. Here we study the clonal evolution of barcoded glioblastoma cells in an unbiased way following serial xenotransplantation to define their(More)
bla(SHV) genes from Escherichia coli and Salmonella enterica isolates from chicken (n = 19) and pork (n = 1) were identified as bla(SHV-2) (n = 5) or bla(SHV-2a) (n = 15). Eighteen were on plasmids of the incI1 (n = 15), incP (n = 2), and incFIB (n = 1) incompatibility groups. These plasmids were all transferable by conjugation between E. coli and S.(More)
Glioblastoma growth is driven by cancer cells that have stem cell properties, but molecular determinants of their tumorigenic behavior are poorly defined. In cancer, altered activity of the epigeneticmodifiers Polycomband Trithorax complexes may contribute to the neoplastic phenotype. Here, we provide the first mechanistic insights into the role of the(More)
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