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Systems Pharmacology Dissection of Cholesterol Regulation Reveals Determinants of Large Pharmacodynamic Variability between Cell Lines

Blattmann, Peter, Henriques, David, Zimmermann, Michael, Frommelt, Fabian, Sauer, Uwe, Saez-Rodriguez, Julio, Aebersold, Ruedi·2017·Cell Systems
DOI 10.1016/j.cels.2017.11.002PMC PMC5747350
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  • HuH7 cells are widely used as a model of hepatocyte LDL uptake and exhibit functional regulatory networks of cholesterol regulation and uptake, SREBP regulation, and statin sensitivity.

    “HuH7 cells, originally derived from a well-differentiated human hepatocellular carcinoma [15], are widely used as a model of hepatocyte LDL uptake and exhibit functional regulatory networks of cholesterol regulation and uptake, SREBP regulation, and statin sensitivity[16].”

    From Genome-scale CRISPR screening for modifiers of cellular LDL uptake (2021) · cites this paper as [16]

    The Results sections describe Huh7 as a well-established liver-derived model for drug response and metabolism, and show functional cholesterol regulation, SREBP2 responses, cholesterol uptake capacity, and statin sensitivity (pages not provided). They do not establish that Huh7 is widely used specifically as a model of hepatocyte LDL uptake. The Discussion cautions that Huh7 relies more on cholesterol synthesis than in vivo hepatocytes and that its predicted uptake behavior still needs experimental confirmation. (LLM, conf=0.85)

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  • HuH7 cells have been shown to serve as excellent models for lipoprotein uptake by hepatocytes.

    “Second, although HuH7 cells have been shown to serve as excellent models for lipoprotein uptake by hepatocytes92, the expression of any single gene may vary from its in vivo state in hepatocytes, potentially leading to a false negative result if a putative Lp(a) receptor is poorly expressed.”

    From Functional interrogation of cellular Lp(a) uptake by genome-scale CRISPR screening (2025) · cites this paper as [92]

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Metadata

Authors
Blattmann, P., Henriques, D., Zimmermann, M., Frommelt, F., Sauer, U., Saez-Rodriguez, J., & Aebersold, R.
Venue
Cell Systems
Publisher
Elsevier BV
Published
2017-12
Volume
5
Issue
6
Pages
604-619.e7
ISSN
2405-4712
DOI
10.1016/j.cels.2017.11.002
PMC
PMC5747350
Cited by
26
References
3
Language
en
Licence
Funders
  • SystemsX.ch
  • Swiss National Science Foundation (3100A0-688 107679)
  • European Research Council (ERC-2008-AdG 233226, ERC-2014-AdG 670821)
  • ETH Zurich

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