Generation of dopaminergic neurons and pigmented epithelia from primate ES cells by stromal cell-derived inducing activity
Open accessAbstract
We previously identified a stromal cell-derived inducing activity (SDIA), which induces differentiation of neural cells, including midbrain tyrosine hydroxylase-positive (TH(+)) dopaminergic neurons, from mouse embryonic stem cells. We report here that SDIA induces efficient neural differentiation also in primate embryonic stem cells. Induced neurons contain TH(+) neurons at a frequency of 35% and produce a significant amount of dopamine. Interestingly, differentiation of TH(+) neurons from undifferentiated embryonic cells occurs much faster in vitro (10 days) than it does in the embryo (approximately 5 weeks). In addition, 8% of the colonies contain large patches of Pax6(+)-pigmented epithelium of the retina. The SDIA method provides an unlimited source of primate cells for the study of pathogenesis, drug development, and transplantation in degenerative diseases such as Parkinson's disease and retinitis pigmentosa.
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ESCs and iPSCs can spontaneously differentiate along the neural lineage and then to RPE cells, which are readily identified by pigmentation and cobblestone appearance.
“ESCs and iPSCs can spontaneously differentiate along the neural lineage, and then to RPE cells, which are readily identified by virtue of pigmentation and cobblestone appearance (Kawasaki et al., 2002; Buchholz et al., 2009) (Fig. 4).”
From The cell biology of the retinal pigment epithelium (2020) · cites this paper as Kawasaki et al., 2002
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- Authors
- Kawasaki, H., Suemori, H., Mizuseki, K., Watanabe, K., Urano, F., Ichinose, H., Haruta, M., Takahashi, M., Yoshikawa, K., Nishikawa, S.-I., Nakatsuji, N., & Sasai, Y.
- Affiliations
- Fujita Health University (JP)
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2002-01-29
- Volume
- 99
- Issue
- 3
- Pages
- 1580-1585
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC122233
- OpenAlex
- W2161264600
- Cited by
- 477
- References
- 41
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 6 · 2023: 10 · 2022: 10 · 2021: 11 · 2020: 12 · 2019: 8 · 2018: 10 · 2017: 20 · 2016: 7 · 2015: 13 · 2014: 17 · 2013: 20 · 2012: 26
- FWCI
- 13.36
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Institutional Repositories DataBase (IRDB) (submittedVersion)
- Tokyo Tech Research Repository (Tokyo Institute of Technology) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- primate embryonic stem cells, dopaminergic neurons, tyrosine hydroxylase, neuronal differentiation, retinal pigment epithelium, Pax6, dopamine synthesis, Parkinson's disease, retinitis pigmentosa, cell transplantation
- MeSH terms
- Animals, Cell Differentiation, Cells, Cultured, Dopamine, Epithelial Cells, Macaca fascicularis, Neurons, Primates, Stem Cells, Time Factors, Transplantation, Heterologous, Tyrosine 3-Monooxygenase, Biomarkers, Mice, SCID, Stromal Cells, Cell Transplantation, Neural Cell Adhesion Molecules, Reverse Transcriptase Polymerase Chain Reaction, Mice
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