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Chunk #32 — DISCUSSION

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Large, Diverse Population Cohorts of hiPSCs and Derived Hepatocyte-like Cells Reveal Functional Genetic Variation at Blood Lipid-Associated Loci.
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Efforts such as the GTEx project (The GTEx Consortium, 2015; Aguet et al., 2016) seek to identify functional eGenes, but these studies rely on scarce primary tissues from postmortem donors or from surgical patients, and the tissues typically represent mixes of different cell types, potentially obscuring eGenes with functional significance in one of the cell types. The distinction between postmortem whole-liver samples and primary human hepatocytes was quite apparent in the global gene expression profiling (Figure S2B). In principle, iPSCs offer an alternative, more expedient approach to eQTL/ASE studies because they can be obtained from healthy living donors non-invasively, are expandable in vitro, and can be differentiated to a single desired cell type. However, a serious shortcoming of in vitro iPSC-differentiated hepatocytes—and, generally, all in vitro iPSC-differentiated cells—is that the resulting cells are immature, heterogeneous, and lack some characteristics of authentic cells in their natural environment in vivo (Schwartz et al., 2014). As with the liver samples, the distinction between HLCs and primary hepatocytes was evident with respect to global gene expression profiling (Figure S3) as well as the expression