Cited by 89Developmental Biology and Gene RegulationPluripotent Stem Cells ResearchTGF-β signaling in diseases

BMP signaling induces visceral endoderm differentiation of XEN cells and parietal endoderm

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Paca, Agnieszka, Séguin, Cheryle A., Clements, Melanie, Ryczko, Michael, Rossant, Janet, Rodriguez, Tristan A., Kunath, Tilo·2012·Developmental Biology

Abstract

The extraembryonic endoderm of mammals is essential for nutritive support of the fetus and patterning of the early embryo. Visceral and parietal endoderm are major subtypes of this lineage with the former exhibiting most, if not all, of the embryonic patterning properties. Extraembryonic endoderm (XEN) cell lines derived from the primitive endoderm of mouse blastocysts represent a cell culture model of this lineage, but are biased towards parietal endoderm in culture and in chimeras. In an effort to promote XEN cells to adopt visceral endoderm character we have mimicked different aspects of the in vivo environment. We found that BMP signaling promoted a mesenchymal-to-epithelial transition of XEN cells with up-regulation of E-cadherin and down-regulation of vimentin. Gene expression analysis showed the differentiated XEN cells most resembled extraembryonic visceral endoderm (exVE), a subtype of VE covering the extraembryonic ectoderm in the early embryo, and during gastrulation it combines with extraembryonic mesoderm to form the definitive yolk sac. We found that laminin, a major component of the extracellular matrix in the early embryo, synergised with BMP to promote highly efficient conversion of XEN cells to exVE. Inhibition of BMP signaling with the chemical inhibitor, Dorsomorphin, prevented this conversion suggesting that Smad1/5/8 activity is critical for exVE induction of XEN cells. Finally, we show that applying our new culture conditions to freshly isolated parietal endoderm (PE) from Reichert's membrane promoted VE differentiation showing that the PE is developmentally plastic and can be reprogrammed to a VE state in response to BMP. Generation of visceral endoderm from XEN cells uncovers the true potential of these blastocyst-derived cells and is a significant step towards modelling early developmental events ex vivo.

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Crossref · 10.1016/j.ydbio.2011.10.013

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  • emVE represents a specialized variant of exVE, perhaps modulating a transcriptional program in response to stimuli such as BMP or Nodal.

    “Differential expression between bulk RNA sequenced E7.5 exVE and emVE populations suggested that emVE represents a specialized variant of exVE (Extended Data Fig. 7d), perhaps modulating a transcriptional program in response to stimuli, such as BMP or Nodal38–40.”

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Authors
Paca, A., Séguin, C. A., Clements, M., Ryczko, M., Rossant, J., Rodriguez, T. A., & Kunath, T.
Affiliations
  • MRC Centre for Regenerative Medicine (GB)
  • Hospital for Sick Children (CA)
  • Hammersmith Hospital (GB)
Corresponding author
Kunath, Tilo
Venue
Developmental Biology
Publisher
Elsevier BV
Published
2012-01
Volume
361
Issue
1
Pages
90-102
ISSN
0012-1606 (ISSN-L)
OpenAlex
W2119250654
Cited by
87
References
103
Citations by year
2026: 4 · 2025: 5 · 2024: 8 · 2023: 8 · 2022: 7 · 2021: 5 · 2020: 7 · 2019: 6 · 2018: 7 · 2017: 6 · 2016: 7 · 2015: 3 · 2014: 4 · 2013: 6 · 2012: 4
FWCI
1.81
Type
journal article
Language
en
Open access
Locations
  • Developmental Biology (publishedVersion)
  • PubMed (publishedVersion)
  • Scholarship@Western (Western University) (submittedVersion)
Funders
  • Pfizer
  • Biotechnology and Biological Sciences Research Council
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
Keywords
BMP signaling, parietal endoderm, extraembryonic endoderm, mesenchymal-epithelial transition, E-cadherin, vimentin, laminin, Smad1/5/8, compound C, Reichert's membrane, yolk sac, developmental plasticity
MeSH terms
Animals, Cell Differentiation, Cell Line, Endoderm, Epithelial Cells, Extracellular Matrix, Flow Cytometry, Fluorescent Antibody Technique, Laminin, Mesoderm, Pyrazoles, Pyrimidines, Vimentin, Signal Transduction, Cadherins, Gene Expression Regulation, Developmental, Cell Culture Techniques, Reverse Transcriptase Polymerase Chain Reaction, Microarray Analysis, Mice, Bone Morphogenetic Protein 4

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