The stem cell/progenitor niche in the regenerating liver (360G-Wellcome-105375_Z_14_A)

£43,595

The formation of liver tissue during embryogenesis requires dynamic interactions with endo the lial and mesenchymal cells of the microenvironment, which can be recapitulated in vitro to direct the production of hepatocytes from pluripotent stem cells. The adult liver is characterised by low cellular turnover, yet it is endowed with a facultative Lgr5+ stem/progenitor population that drives tissue regeneration following damage and can be expanded in vitro as 3D liver organoids. Here, we aim to study adult non-parenchymal liver lineages – liver sinusoidal endothelial cells, hepatic stellate cells, portal myofibroblasts and Kupffer cells – as functional components of the microenvironment, or ‘niche’, in progenitor -mediated regeneration. We will characterise the spatiotemporal association of putative niche cells with Lgr5+ progenitors and differentiated progeny throughout regeneration, and perform a whole-genome transcriptomic analysis on selected niche lineages. Making use of organoid co-cultures that incorporate niche cells from regenerating livers, we will validate the ability of the niche to support Lgr5+ progenitor proliferation and differentiation. The molecular effectors of the pro-differentiation niche will be identified and the cells will be ablated in transgenic mice to confirm their niche role in vivo. These studies may elucidate novel mechanisms of liver healing and result in the establishment of organotypic liver cultures.

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Grant Details

Amount Awarded 43595
Applicant Surname Cordero Espinoza
Approval Committee Internal Decision Panel for C&S
Award Date 2016-09-30T00:00:00+00:00
Financial Year 2015/16
Grant Programme: Title PhD Studentship (Basic)
Internal ID 105375/Z/14/A
Lead Applicant Miss Lucia Cordero Espinoza
Partnership Value 43595
Planned Dates: End Date 2018-09-30T00:00:00+00:00
Planned Dates: Start Date 2015-10-01T00:00:00+00:00
Recipient Org: Country United Kingdom
Region East of England
Sponsor(s) Prof Austin Smith