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SUMMARY:Transcriptional characterization of glioma stem cells using high-t
 hroughput tag sequencing - Paul Bertone (EBI)
DTSTART:20101004T150000Z
DTEND:20101004T160000Z
UID:TALK24782@talks.cam.ac.uk
CONTACT:Florian Markowetz
DESCRIPTION:A recent advance in the study of glioblastoma multiforme (GBM)
  is the establishment of glioma-derived neural stem (GNS) cells that may r
 epresent the glioma cell of origin. These exhibit many similarities to nor
 mal neural stem (NS) cells and are propagated as a uniform\, adherent mono
 layer culture to effectively suppress differentiation. GNS cells to give r
 ise to authentic glioma tumors when xenografted in immunocompromised NOD/S
 CID mice\, yet both normal and diseased counterparts are morphologically a
 nd immunohistologically indistinguishable. \n\nTo characterize the transc
 riptome of GNS cells and identify transcriptional differences between GNS 
 and NS that may underlie tumorigenesis\, we carried out high-throughput se
 quencing of mRNA tags (Tag-Seq) on GNS lines from three histologically dis
 tinct gliomas and on two normal NS lines. Technical reproducibility of cel
 l line establishment and tag sequencing was high\, as demonstrated by comp
 arison of Tag-Seq results for two independently established GNS lines from
  the same parental tumor. Applying stringent criteria\, we identified a se
 t of 80 genes consistently up- or down-regulated among the GNS lines relat
 ive to the NS lines by a factor of two of more. This set contains known gl
 ioma-related genes\, e.g. PTEN\, as well as novel candidates\, several wit
 h known regulatory functions in other contexts. \n\nIn addition to mRNA e
 xpression\, we detected differential expression of a number of noncoding R
 NA transcripts between GNS and NS lines\, including several from loci neig
 hboring known regulatory genes\, e.g. the HOXA cluster. We also mapped chr
 omosomal aberrations in the GNS lines by array comparative genomic hybridi
 zation (aCGH). On a global level we see a correlation between chromosomal 
 aberrations and expression levels\, but this trend was modest\, suggesting
  that regulatory changes and post-transcriptional factors not related to t
 he cancer genome architecture play a major role in shaping the GNS transcr
 iptome. 
LOCATION:Cancer Research UK Cambridge Research Institute\, Lecture Theatre
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