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SUMMARY:LMB Seminar Series - Stem cells\, regeneration and organoid cultur
 es - Meritxell Huch\, Wellcome Sir Henry Dale Fellow\, Member of the Depar
 tment of Physiology\, Development and Neuroscience
DTSTART:20190228T160000Z
DTEND:20190228T170000Z
UID:TALK116629@talks.cam.ac.uk
CONTACT:72112
DESCRIPTION:Stem cells\, regeneration and organoid cultures\n\nMeritxell H
 uch(1\,2\,3)\n\n1: Gurdon Institute-Wellcome Trust/ Cancer Research UK\, C
 B2 1QN United Kingdom\n2: Department of Physiology\, Developmental Biology
  and Neuroscience\, University of Cambridge\, \n3: the Wellcome Trust-Medi
 cal Research Council Stem Cell Institute\n\nWe reported that mouse liver o
 rganoids indefinitely expanded in vitro (for >1 year)\, in the absence of 
 a mesenchymal niche. The cultured cells expressed ductal markers and diffe
 rentiated into functional hepatocytes in vitro and in vivo\, following tra
 nsplantation. We further developed our culture system to study human liver
  biology and disease. Hence\, human liver organoids from liver donor tissu
 e expand long term in culture while maintaining their differentiation pote
 ntial and genetic stability in vitro. Recently we demonstrated the applica
 bility of this system to study human liver cancer in vitro. We established
  the first human liver cancer organoid culture system for both hepatocellu
 lar carcinoma as well as cholangiocarcinoma resected material\, and demons
 trated its applicability for disease modeling and drug testing. Here\, we 
 discuss the use of this liver organoid technology to underscore biological
  principles of adult liver regeneration. Upon severe or chronic liver inju
 ry\, differentiated adult liver cholangiocytes (ductal cells) become activ
 ated and proliferate extensively to restore the tissue\, by generating bot
 h hepatocytes and ductal cells. However\, the molecular mechanism behind t
 he activation of ductal cells remains largely unknown. Here we report that
  our organoid culture system enables the activation of adult differentiate
 d liver ductal cells into bi-potent liver progenitors\, hence providing a 
 platform where to study regeneration in a dish. Using this liver organoid 
 system we have found that the transition from the ductal differentiated st
 ate to an active proliferating progenitor state involves a massive\, yet t
 ransient\, epigenetic reprogramming where active DNA-demethylation plays a
 n important role in order to activate the progenitor program and successfu
 lly establish self-renewing liver organoid cultures. \n
LOCATION:Max Perutz Lecture Theatre\, Medical Research Council (MRC) (MRC 
 Laboratory of Molecular Biol
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