Cited by 68Pluripotent Stem Cells ResearchMesenchymal stem cell researchLiver physiology and pathology

Asialoglycoprotein receptor 1 is a specific cell-surface marker for isolating hepatocytes derived from human pluripotent stem cells

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Peters, Derek T., Henderson, Christopher A., Warren, Curtis R., Friesen, Max, Xia, Fang, Becker, Caroline E., Musunuru, Kiran, Cowan, Chad A.·2016·Development

Abstract

Hepatocyte-like cells (HLCs) are derived from human pluripotent stem cells (hPSCs) in vitro, but differentiation protocols commonly give rise to a heterogeneous mixture of cells. This variability confounds the evaluation of in vitro functional assays performed using HLCs. Increased differentiation efficiency and more accurate approximation of the in vivo hepatocyte gene expression profile would improve the utility of hPSCs. Towards this goal, we demonstrate the purification of a subpopulation of functional HLCs using the hepatocyte surface marker asialoglycoprotein receptor 1 (ASGR1). We analyzed the expression profile of ASGR1-positive cells by microarray, and tested their ability to perform mature hepatocyte functions (albumin and urea secretion, cytochrome activity). By these measures, ASGR1-positive HLCs are enriched for the gene expression profile and functional characteristics of primary hepatocytes compared with unsorted HLCs. We have demonstrated that ASGR1-positive sorting isolates a functional subpopulation of HLCs from among the heterogeneous cellular population produced by directed differentiation.

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  • The differentiation protocol used was developed and optimized from published literature and chosen for its capacity to generate iHLOs with high CYP enzyme activity, particularly CYP3A4.

    “The differentiation protocol utilized was developed and optimized from the published literatures18–21, specifically chosen for its capacity to generate iHLOs with high CYP enzyme activity, particularly CYP3A4, which is crucial for drug metabolism and toxicology evaluations.”

    From ​Temporal proteomic profiling of iPSC-derived human liver organoids reveals optimal maturation for drug metabolism and toxicology (2026) · cites this paper as [20]

    The Results and Discussion (page unavailable) describe an optimized differentiation protocol based on established methods. They also report increased CYP3A4 activity after ASGR1-positive HLCs were sorted and replated, compared with unsorted HLCs. The paper studies HLCs, not iHLOs, and does not say the differentiation protocol was chosen for its capacity to generate iHLOs with high CYP3A4 activity. (LLM, conf=0.88)

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  • The protocol was chosen due to its demonstrated capacity to generate iHLOs with high CYP enzyme activity, particularly CYP3A4.

    “This protocol was chosen due to its demonstrated capacity to generate iHLOs with high CYP enzyme activity, particularly CYP3A4, which is crucial for our subsequent compound or drug metabolism and toxicology evaluations.”

    From ​Temporal proteomic profiling of iPSC-derived human liver organoids reveals optimal maturation for drug metabolism and toxicology (2026) · cites this paper as [20]

    In Results and Discussion (page unavailable), the paper reports significantly higher CYP3A4 activity in ASGR1-enriched, replated hepatocyte-like cells than in unsorted cells. It studies hepatocyte-like cells, not iHLOs, and reports that primary human hepatocytes had substantially higher activity; it therefore does not establish high CYP3A4 activity in iHLOs generated by the chosen protocol. (LLM, conf=0.88)

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Authors
Peters, D. T., Henderson, C. A., Warren, C. R., Friesen, M., Xia, F., Becker, C. E., Musunuru, K., & Cowan, C. A.
Affiliations
  • Harvard University (US)
  • Brigham and Women's Hospital (US)
Corresponding author
Cowan, Chad A.
Venue
Development
Published
2016-05-01
Volume
143
Issue
9
Pages
1475-1481
ISSN
  • 0950-1991 (ISSN-L)
  • 1477-9129
OpenAlex
W2345599021
Cited by
68
References
23
Citations by year
2026: 7 · 2025: 8 · 2024: 6 · 2023: 4 · 2022: 6 · 2021: 8 · 2020: 9 · 2019: 12 · 2018: 3 · 2017: 3 · 2016: 1
FWCI
3.29
Type
journal article
Language
en
Open access
Locations
  • Development (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • HighWire Press Open Archive (submittedVersion)
Funders
  • Harvard Stem Cell Institute
  • National Heart, Lung, and Blood Institute (R21HL120781, U01HL100408, U01HL107440)
  • National Institute of Diabetes and Digestive and Kidney Diseases (R01DK097768, P30DK040561)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
  • Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
  • Health Sciences › Medicine › Hepatology › Liver physiology and pathology
Keywords
ASGR1, hepatocyte-like cells, human pluripotent stem cells, hepatocyte differentiation, cell surface markers, cell sorting, albumin secretion, urea secretion, hepatocyte heterogeneity
MeSH terms
Albumins, Cell Differentiation, Cell Line, Cell Membrane, Cytochromes, Flow Cytometry, Humans, Urea, Hepatocytes, Asialoglycoprotein Receptor, Embryonic Stem Cells, Induced Pluripotent Stem Cells

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