The mesenchymal transcription factor SNAI-1 instructs human liver specification
Open accessAbstract
Epithelial-mesenchymal transition (EMT) and the mesenchymal-epithelial transition (MET) are processes required for embryo organogenesis. Liver develops from the epithelial foregut endoderm from which the liver progenitors, hepatoblasts, are specified. The migrating hepatoblasts acquire a mesenchymal phenotype to form the liver bud. In mid-gestation, hepatoblasts mature into epithelial structures: the hepatocyte cords and biliary ducts. While EMT has been associated with liver bud formation, nothing is known about its contribution to hepatic specification. We previously established an efficient protocol from human embryonic stem cells (hESC) to generate hepatic cells (Hep cells) resembling the hepatoblasts expressing alpha-fetoprotein (AFP) and albumin (ALB). Here we show that Hep cells express both epithelial (EpCAM and E-cadherin) and mesenchymal (vimentin and SNAI-1) markers. Similar epithelial and mesenchymal hepatoblasts were identified in human and mouse fetal livers, suggesting a conserved interspecies phenotype. Knock-down experiments demonstrated the importance of SNAI-1 in Hep cell hepatic specification. Moreover, ChIP assays revealed direct binding of SNAI-1 in the promoters of AFP and ALB genes consistent with its transcriptional activator function in hepatic specification. Altogether, our hESC-derived Hep cell cultures reveal the dual mesenchymal and epithelial phenotype of hepatoblast-like cells and support the unexpected transcriptional activator role of SNAI-1 in hepatic specification.
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Epithelial-mesenchymal plasticity has been previously identified within hepatic tissues and cell lines.
“epithelial-mesenchymal plasticity has been previously identified within hepatic tissues and cell lines”
From Single-Cell Transcriptomics Reveals Early Emergence of Liver Parenchymal and Non-parenchymal Cell Lineages (2020) · cites this paper as Goldman et al., 2016
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- Authors
- Goldman, O., Valdes, V. J., Ezhkova, E., & Gouon-Evans, V.
- Affiliations
- Icahn School of Medicine at Mount Sinai (US)
- Venue
- Stem Cell Research
- Publisher
- Elsevier BV
- Published
- 2016-07
- Volume
- 17
- Issue
- 1
- Pages
- 62-68
- ISSN
- 1873-5061 (ISSN-L)
- PMC
- PMC5012916
- OpenAlex
- W2397639975
- Cited by
- 8
- References
- 28
- Citations by year
- 2021: 4 · 2020: 2 · 2017: 2
- FWCI
- 0.35
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Stem Cell Research (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion, cc-by-nc-nd)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Black Family Stem Cell Institute
- National Institute of Diabetes and Digestive
- Kidney Diseases for the mouse study (R01DK087867-01)
- March of Dimes (FY113-969)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR063724)
- The Pew Charitable Trusts (00026199)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Keywords
- hepatoblasts, epithelial-mesenchymal transition, mesenchymal-epithelial transition, human embryonic stem cells, liver development, alpha-fetoprotein, albumin, transcriptional activation, foregut endoderm, fetal liver
- MeSH terms
- Snail Family Transcription Factors, Epithelial Cell Adhesion Molecule, Animals, Cell Differentiation, Fetus, Humans, Liver, Microscopy, Fluorescence, Vimentin, Cadherins, Hepatocytes, RNA Interference, RNA, Small Interfering, Chromatin Immunoprecipitation, Mice, Real-Time Polymerase Chain Reaction
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