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2021 (English)In: Journal of Cellular Physiology, ISSN 0021-9541, E-ISSN 1097-4652, Vol. 236, no 8, p. 5885-5894Article in journal (Refereed) Published
Abstract [en]
Human hepatocytes show marked differences in cell size, gene expression, and function throughout the liver lobules, an arrangement termed liver zonation. However, it is not clear if these zonal size differences, and the associated phenotypic differences, are retained in isolated human hepatocytes, the “gold standard” for in vitro studies of human liver function. Here, we therefore explored size differences among isolated human hepatocytes and investigated whether separation by size can be used to study liver zonation in vitro. We used counterflow centrifugal elutriation to separate cells into different size fractions and analyzed them with label-free quantitative proteomics, which revealed an enrichment of 151 and 758 proteins (out of 5163) in small and large hepatocytes, respectively. Further analysis showed that protein abundances in different hepatocyte size fractions recapitulated the in vivo expression patterns of previously described zonal markers and biological processes. We also found that the expression of zone-specific cytochrome P450 enzymes correlated with their metabolic activity in the different fractions. In summary, our results show that differences in hepatocyte size matches zonal expression patterns, and that our size fractionation approach can be used to study zone-specific liver functions in vitro.
Place, publisher, year, edition, pages
John Wiley & Sons, 2021
National Category
Pharmaceutical Sciences
Identifiers
urn:nbn:se:uu:diva-382404 (URN)10.1002/jcp.30273 (DOI)000608176800001 ()
Funder
Swedish Research Council, 2822, 01951
2019-04-242019-04-242021-08-13Bibliographically approved