ArticleMolecular metabolism2017
A high-content small molecule screen identifies novel inducers of definitive endoderm.
Article in Molecular metabolism, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 40 citations in OpenAlex.
- Review
- SOX17 in pulmonary arterial hypertension: from development to clinical phenotype.European respiratory review : an official journal of the European Respiratory Society · 2025Review
- Chemically defined and growth factor-free system for highly efficient endoderm induction of human pluripotent stem cells.Stem cell reports · 2025Article
- From stem cells to pancreatic β-cells: strategies, applications, and potential treatments for diabetes.Molecular and cellular biochemistry · 2025Review
- Fasudil and viscosity of gelatin promote hepatic differentiation by regulating organelles in human umbilical cord matrix-mesenchymal stem cells.Stem cell research & therapy · 2024Article
- In silico discovery of small molecules for efficient stem cell differentiation into definitive endoderm.Stem cell reports · 2023Article
- Rapid and robust directed differentiation of mouse epiblast stem cells into definitive endoderm and forebrain organoids.Development (Cambridge, England) · 2022Article
- Stem Cell-Derived Islets for Type 2 Diabetes.International journal of molecular sciences · 2022Review
- Efficiently generate functional hepatic cells from human pluripotent stem cells by complete small-molecule strategy.Stem cell research & therapy · 2022Article
- Article
- Engineering islets from stem cells for advanced therapies of diabetes.Nature reviews. Drug discovery · 2021Review
- Automated optimization of endoderm differentiation on chip.Lab on a chip · 2021Article
- Early patterning of ABCB, ABCC, and ABCG transporters establishes unique territories of small molecule transport in embryonic mesoderm and endoderm.Developmental biology · 2021Article
- Phenotypic technologies in stem cell biology.Cell chemical biology · 2021Review
- Differentiation of Human Pluripotent Stem Cells Into Definitive Endoderm Cells in Various Flexible Three-Dimensional Cell Culture Systems: Possibilities and Limitations.Frontiers in cell and developmental biology · 2021Article
- Review
- Hepatogenic Potential and Liver Regeneration Effect of Human Liver-derived Mesenchymal-Like Stem Cells.Cells · 2020Article
- Small Molecule-Induced Pancreatic β-Like Cell Development: Mechanistic Approaches and Available Strategies.International journal of molecular sciences · 2020Review
- Article
- Functions of stem cells of thyroid glands in health and disease.Reviews in endocrine & metabolic disorders · 2019Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectivesHuman embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs) can generate any given cell type in the human body. One challenge for cell-replacement therapy is the efficient differentiation and expansion of large quantities of progenitor cells from pluripotent stem cells produced under good manufacturing practice (GMP). FOXA2 and SOX17 double positive definitive endoderm (DE) progenitor cells can give rise to all endoderm-derived cell types in the thymus, thyroid, lung, pancreas, liver, and gastrointestinal tract. FOXA2 is a pioneer transcription factor in DE differentiation that is also expressed and functionally required during pancreas development and islet cell homeostasis. Current differentiation protocols can successfully generate endoderm; however, generation of mature glucose-sensitive and insulin-secreting β-cells is still a challenge. As a result, it is of utmost importance to screen for small molecules that can improve DE and islet cell differentiation for cell-replacement therapy for diabetic patients.
methodsThe aim of this study was to identify and validate small molecules that can induce DE differentiation and further enhance pancreatic progenitor differentiation. Therefore, we developed a large scale, high-content screen for testing a chemical library of 23,406 small molecules to identify compounds that induce FoxA2 in mouse embryonic stem cells (mESCs).
resultsBased on our high-content screen algorithm, we selected 84 compounds that directed differentiation of mESCs towards the FoxA2 lineage. Strikingly, we identified ROCK inhibition (ROCKi) as a novel mechanism of endoderm induction in mESCs and hESCs. DE induced by the ROCK inhibitor Fasudil efficiently gives rise to PDX1
conclusionTaken together, DE induction by ROCKi can simplify and improve current endoderm and pancreatic differentiation protocols towards a GMP-grade cell product for β-cell replacement.
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