Expression of Tight Junction Components in Hepatocyte-Like Cells Differentiated from Human Embryonic Stem Cells

Boglárka Erdélyi-Belle, György Török, A. Apáti, B. Sarkadi, Z. Schaff, András Kiss, L. Homolya

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Human embryonic stem cells can be differentiated in vitro into a wide variety of progeny cells by addition of different morphogens and growth factors. Our aim was to monitor the expression pattern of tight junction (TJ) components and various cellular markers during differentiation of stem cell lines toward the hepatic lineage. Human embryonic stem cell lines (HUES1, HUES9) were differentiated into endoderm-like cells, and further differentiated to hepatocyte-like cells. Gene expressions of Oct3/4, Nanog, alpha-fetoprotein, albumin, cytokeratins (CK-7, CK-8, CK-18, CK-19), ATP-binding cassette (ABC) transporters (ABCC2, ABCC7, ABCG2), and various TJ components, including claudin-1, claudin-4, claudin-5, claudin-7, and tricellulin, as well as an extracellular matrix component, agrin were monitored during hepatic differentiation by real-time quantitative PCR. The differentiated cells exhibit epithelial morphology and functional assessments similar to that of hepatocytes. The expression level of stem cell marker genes (Oct3/4 and Nanog) significantly and gradually decreased, while liver-associated genes (alpha-fetoprotein, albumin) reached their highest expression at the end of the differentiation. The endoderm-like cells expressed claudin-1, which declined eventually. The expression levels of cholangiocyte markers including claudin-4, CK-7, CK-19, and agrin gradually increased and reached their highest level at the final stage of differentiation. In contrast, these cells did not express notable level of claudin-7, CK-8 and tricellulin. The marker set used for monitoring differentiation revealed both hepatocyte and cholangiocyte characteristics of the differentiated cells at the final stage. This is the first report describing the expression level changes of various TJ components, and underlining their importance in hepatic differentiation.

Original languageEnglish
Pages (from-to)1059-1070
Number of pages12
JournalPathology and Oncology Research
Volume21
Issue number4
DOIs
Publication statusPublished - Apr 7 2015

Fingerprint

Tight Junctions
Hepatocytes
MARVEL Domain Containing 2 Protein
Claudin-4
Agrin
Claudin-1
Endoderm
Liver
alpha-Fetoproteins
Stem Cells
Claudin-5
Keratin-7
Cell Line
ATP-Binding Cassette Transporters
Differentiation Antigens
Genes
Extracellular Matrix
Human Embryonic Stem Cells
Real-Time Polymerase Chain Reaction
Intercellular Signaling Peptides and Proteins

Keywords

  • Agrin
  • Claudins
  • Cytokeratins
  • Human embryonic stem cells
  • Stem cell differentiation
  • Tight junctions
  • Tricellulin

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Pathology and Forensic Medicine

Cite this

Expression of Tight Junction Components in Hepatocyte-Like Cells Differentiated from Human Embryonic Stem Cells. / Erdélyi-Belle, Boglárka; Török, György; Apáti, A.; Sarkadi, B.; Schaff, Z.; Kiss, András; Homolya, L.

In: Pathology and Oncology Research, Vol. 21, No. 4, 07.04.2015, p. 1059-1070.

Research output: Contribution to journalArticle

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