title: Asialoglycoprotein receptor 1 is a specific cell-surface marker for isolating hepatocytes derived from human pluripotent stem cells.
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.
authors.affiliation: Department of Stem Cell and Regenerative Biology and Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Derek T
authors.initials: DT
authors.lastname: Peters
authors.affiliation: Department of Stem Cell and Regenerative Biology and Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA.
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Henderson
authors.affiliation: Department of Stem Cell and Regenerative Biology and Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA.
authors.forename: Curtis R
authors.initials: CR
authors.lastname: Warren
authors.affiliation: Department of Stem Cell and Regenerative Biology and Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA.
authors.forename: Max
authors.initials: M
authors.lastname: Friesen
authors.affiliation: Department of Stem Cell and Regenerative Biology and Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA.
authors.forename: Fang
authors.initials: F
authors.lastname: Xia
authors.affiliation: Department of Stem Cell and Regenerative Biology and Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA.
authors.forename: Caroline E
authors.initials: CE
authors.lastname: Becker
authors.affiliation: Department of Stem Cell and Regenerative Biology and Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.
authors.forename: Kiran
authors.initials: K
authors.lastname: Musunuru
authors.affiliation: Department of Stem Cell and Regenerative Biology and Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA 02114, USA chad_cowan@harvard.edu.
authors.forename: Chad A
authors.initials: CA
authors.lastname: Cowan
mesh_terms: D000418:Albumins / Q000378:metabolism; D037263:Asialoglycoprotein Receptor / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D003580:Cytochromes / Q000378:metabolism; D053595:Embryonic Stem Cells / Q000166:cytology*; D005434:Flow Cytometry / Q000379:methods*; D022781:Hepatocytes / Q000378:metabolism*; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology*; D014508:Urea / Q000378:metabolism
chemical_list: C546927:ASGR1 protein, human; D000418:Albumins; D037263:Asialoglycoprotein Receptor; D003580:Cytochromes; D014508:Urea
keywords: FACS; Hepatocytes; Human pluripotent stem cells; MACS; Transcriptomics