Monitoring and robust induction of nephrogenic intermediate mesoderm from human pluripotent stem cells
Open accessAbstract
A method for stimulating the differentiation of human pluripotent stem cells into kidney lineages remains to be developed. Most cells in kidney are derived from an embryonic germ layer known as intermediate mesoderm. Here we show the establishment of an efficient system of homologous recombination in human pluripotent stem cells by means of bacterial artificial chromosome-based vectors and single-nucleotide polymorphism array-based detection. This system allowed us to generate human-induced pluripotent stem cell lines containing green fluorescence protein knocked into OSR1, a specific intermediate mesoderm marker. We have also established a robust induction protocol for intermediate mesoderm, which produces up to 90% OSR1(+) cells. These human intermediate mesoderm cells can differentiate into multiple cell types of intermediate mesoderm-derived organs in vitro and in vivo, thereby supplying a useful system to elucidate the mechanisms of intermediate mesoderm development and potentially providing a cell source for regenerative therapies of the kidney.
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Spatiotemporal presentation of soluble cues is especially important for growing human iPSC into complex structures with multiple cell lineages, such as kidney organoids.
“The importance of presenting soluble cues in a spatiotemporally relevant manner is especially important for growing human iPSC into complex structures with multiple cell lineages such as in the case of kidney organoids83.”
From Organoids (2022) · cites this paper as [83]
The Results (Establishment of robust induction methods of IM cells; page unavailable) show that sequential growth-factor treatments improve induction of intermediate mesoderm from human pluripotent stem cells, supporting the importance of cue timing. But the paper does not establish spatial presentation of cues as important for growing kidney organoids. The Discussion (page unavailable) says production of three-dimensional renal structures remained inefficient. (LLM, conf=0.86)
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- Authors
- Mae, S.-I., Shono, A., Shiota, F., Yasuno, T., Kajiwara, M., Gotoda-Nishimura, N., Arai, S., Sato-Otubo, A., Toyoda, T., Takahashi, K., Nakayama, N., Cowan, C. A., Aoi, T., Ogawa, S., McMahon, A. P., Yamanaka, S., & Osafune, K.
- Affiliations
- Kyoto University (JP)
- Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases (US)
- Harvard University (US)
- The University of Tokyo (JP)
- University of Southern California (US)
- Gladstone Institutes (US)
- Corresponding author
- Osafune, Kenji
- ORCID
- Venue
- Nature Communications
- Published
- 2013-01-22
- Volume
- 4
- Issue
- 1
- Pages
- 1367-1367
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC4447148
- OpenAlex
- W2000714884
- Cited by
- 291
- References
- 36
- Citations by year
- 2026: 5 · 2025: 6 · 2024: 9 · 2023: 10 · 2022: 16 · 2021: 21 · 2020: 18 · 2019: 20 · 2018: 22 · 2017: 28 · 2016: 39 · 2015: 44 · 2014: 33 · 2013: 20
- FWCI
- 20.29
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Nature Communications (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Kyoto University Research Information Repository (Kyoto University) (submittedVersion)
- Funders
- Takeda Science Foundation
- Uehara Memorial Foundation
- Ministry of Education, Culture, Sports, Science and Technology
- National Institutes of Health (DK054364)
- Japan Society for the Promotion of Science (23791200)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK054364, [DK054364, R37DK054364)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Renal and related cancers
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- human pluripotent stem cells, induced pluripotent stem cells, kidney development, OSR1, homologous recombination, single nucleotide polymorphism array, renal differentiation, tubular structures, kidney regeneration
- MeSH terms
- Animals, Cell Differentiation, Cell Line, Flow Cytometry, Humans, Kidney, Mesoderm, Time Factors, Protein Serine-Threonine Kinases, Gene Targeting, Gene Expression Regulation, Developmental, Gene Dosage, Polymorphism, Single Nucleotide, Green Fluorescent Proteins, Mice, Embryonic Stem Cells, Gene Knock-In Techniques, Genetic Loci, Induced Pluripotent Stem Cells, Embryoid Bodies
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