The Integrative Liver Cell Core (ILCC) strives to serve the scientific community of alcoholic liver
disease (ALD) and cirrhosis via specialized services of isolating 6 different liver cell types
(hepatocytes, HC; hepatic macrophages, HM; hepatic stellate cells, HSC; sinusoidal endothelial
cells, SEC; mesothelial cells, MC; and CD133+ ductular reaction progenitors, DRP) from 12 different
ALD and liver fibrosis models which reproduce wide and specific spectra of liver diseases.
To support leading-edge cell type specific research, the ILCC also couples these isolation
procedures with innovative techniques: 1) Rosa26-reporter mouse-based genetic lineage and cell fate
tracing for HC, DRP, HSC, and HM in ALD and alcohol-promoter liver tumor; 2) fluorescence-
activated cell sorting (FACS)-based analysis of resident vs. migrating HM to assess their relative
contributions to alcoholic steatohepatitis; 3) FACS-based isolation of vitamin A+/Col1a1- quiescent
HSC, vitamin A+/Col1a1+ activated HSC, and vitamin A-/Col1a1+ mesenchymal cells from mouse
ALD models; and 5) FACS isolation of CD133+ tumor-initiating stem cell-like cells and DRP from
alcohol-promoted liver tumor and alcoholic hepatitis. To achieve these integrative services, the ILCC
closely collaborates with the Animal Core of the P50 Alcohol Center and supports genetic loss or gain
of function approaches at each specific cellular level in mouse models of chronic alcoholic
steatohepatitis, alcoholic hepatitis, alcoholic liver fibrosis, and alcohol-promoted liver tumor.
Since the last renewal submission, the ILCC served 41 investigators from 25 institutions by
performing 1,151 isolation preparations and providing 283 Cell Bank samples. These efforts
facilitated 34 publications and acquisition or continuation of 20 federal grants plus 2 pending
applications. Of these 41 investigators, 22 were out-of-region investigators and 14 were early career
investigators across the country, attesting that the ILCC contributes as a national resource.
The proposed ILCC renewal aims to continue its unique and cutting-edge services of liver cell
isolation and analysis and to promote genetic, epigenetic, metabolic, and molecular research on
altered cell fate regulation of different liver cell types which manifest as fundamental mechanisms
underlying inflammation, fibrosis, and tumorigenesis in ALD.