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DTSTART:20181028T020000
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DTSTAMP:20260404T110041Z
UID:5c0f84726db3f638908210@ist.ac.at
DTSTART:20181220T133000
DTEND:20181220T143000
DESCRIPTION:Speaker: Martin Leeb\nhosted by Simon Hippenmeyer\nAbstract: Ce
 ll fate changes during embryonic development require the irreversible rewi
 ring of transcription factor networks to establish and stabilise lineage i
 dentity. We use embryonic stem cells as a powerful model to study cell fat
 e decisions.The identity\, function and interactions of the key transcript
 ion factors that maintain ES cell identity are well understood. Much less 
 understood is how this highly recursive transcription factor network is di
 smantled to allow the exit from pluripotency and proper progression toward
 s differentiation.Haploid ES cells provide a platform for unbiased random 
 mutagenesis based screens in mammalian cells. By combining powerful improv
 ed mutagenesis methodologies and efficient protocols for transposon integr
 ation mapping\, we have successfully performed a saturation screen to iden
 tify the key players in the exit from pluripotency. Knowing which genes ar
 e involved in ES cell differentiation does of course not mean understandin
 g what these factors actually do and how they cooperate in mediating diffe
 rentiation. To address this question\, we are following a systems biology 
 approach by analysing the impact of 74 differentiation delaying mutations 
 on the transcriptional state of ES cells during the exit from pluripotency
 . Integrated analysis of these datasets have facilitated the prediction of
  genetic interactions and the derivation of an extended pluripotency speci
 fic genetic network\, for which we can show relevance in vivo.  Surprising
 ly\, our list of candidate genes contained several genes that are involved
  in the regulation of RNA homeostasis. Specifically\, several components o
 f the nonsense mediated mRNA decay (NMD) cascade were found among the top 
 candidates. Indeed\, genetic deficiency for NMD factors results in differe
 ntiation delays without interfering with self-renewal. NMD is a translatio
 n coupled mechanism. Intriguingly\, we find that NMD itself regulates tran
 slation initiation and propose that the deregulation of both transcription
  and translation in NMD mutant cells is responsible for a failure to prope
 rly execute the differentiation programme.
LOCATION:Seminar Room\, Lab Building East\, ISTA
ORGANIZER:lmarr@ist.ac.at
SUMMARY:Martin Leeb: The regulatory principles of embryonic stem cell diffe
 rentiation
URL:https://talks-calendar.ista.ac.at/events/1687
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