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SUMMARY:Cell fate transitions and the secret life of histones - Dr Maria C
 hristophorou
DTSTART:20240226T180000Z
DTEND:20240226T193000Z
UID:TALK210070@talks.cam.ac.uk
CONTACT:Drishtant Chakraborty
DESCRIPTION:The discovery that somatic cells can be reprogrammed to a plur
 ipotent state and instructed to differentiate into various cell types prom
 ises to revolutionise regenerative medicine. We previously demonstrated th
 at the protein post-translational modification citrullination is induced u
 pon the introduction of reprogramming transcription (Yamanaka) factors int
 o somatic cells\, where it precedes and mediates their reprogramming to in
 duced pluripotent stem (iPS) cells. We have since found that the induction
  of citrullination is a general\, evolutionarily conserved feature of cell
  reprogramming and tissue regeneration. The cells that activate citrullina
 tion are mutually exclusive with the iPS cells\, suggesting that they act 
 as “active bystanders” that mediate reprogramming in a non-cell-autono
 mous manner.\n\n \n\nWe have made the unexpected discovery that bystander 
 cells release citrullinated chromatin to the extracellular space\, in a pr
 ocess akin to Neutrophil Extracellular Traps. Blocking of extracellular ch
 romatin components reduces reprogramming\, as does pharmacological interfe
 rence with chromatin sensing\, innate immunity signalling pathways. Extrac
 ellular citrullinated chromatin is also a feature of tissue regeneration. 
 \n\n \n\nOur data suggest that cells that “fail” to reprogramme in fac
 t have an active role in supporting the establishment of pluripotency. Add
 itionally\, they open a new research avenue into the study of extracellula
 r chromatin as a cell communication mechanism that mediates cell fate tran
 sitions and present an opportunity to exploit this mechanism to enhance re
 programming and regeneration while minimizing genetic manipulation.\n\n
LOCATION:Pfizer Lecture Theatre\,  Department of Chemistry\, Lensfield Roa
 d
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