ArticleThe Journal of clinical investigation2020
Congenital pituitary hypoplasia model demonstrates hypothalamic OTX2 regulation of pituitary progenitor cells.
Article in The Journal of clinical investigation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 66 citations in OpenAlex.
- Functional analysis of adrenocorticotropic-hormone-producing pituitary cells derived from human pluripotent stem cells in murine and primate models of hypopituitarism.Stem cell research & therapy · 2026Article
- Diverse SOX3 genetic variants and their associated phenotypic spectrum in human disease.Endocrine reviews · 2026Review
- Emerging human cell-based in vitro models for studying pituitary development and disorders.Endocrine journal · 2026Review
- Emerging applications of human iPSCs in pituitary diseases.Nature reviews. Endocrinology · 2026Article
- Endocrinology at a Miniature Level: Pluripotent Stem-Cell-Derived Organoid Models of Hypothalamus-Pituitary Axes.Biomolecules · 2026Review
- Neurogenesis defects in iPSC-derived midbrain organoids of early-onset Parkinson's disease with 22q11.2 deletion syndrome.Frontiers in cellular neuroscience · 2026Article
- Organoids in Genetic Disorders: from Disease Modeling to Translational Applications.Stem cell reviews and reports · 2025Review
- Modeling of T cell-mediated autoimmune pituitary disease using human induced pluripotent stem cell-originated organoid.Nature communications · 2025Article
- Prediction of the hypothalamus-pituitary organoid formation using machine learning.Cell reports methods · 2025Article
- Genetic models of Cushing's disease : From cells, in vivo transgenic models to human pituitary organoids.Pituitary · 2025Review
- Human Pituitary Organoids: Transcriptional Landscape Deciphered by scRNA-Seq and Stereo-Seq, with Insights into SOX3's Role in Pituitary Development.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Biomedical applications of organoids in genetic diseases.Medical review (2021) · 2025Review
- Modeling corticotroph deficiency with pituitary organoids supports the functional role ofeLife · 2024Article
- Recapitulation and investigation of human brain development with neural organoids.IBRO neuroscience reports · 2024Article
- Guidelines for Manufacturing and Application of Organoids: Brain.International journal of stem cells · 2024Article
- Organoids in endocrine and metabolic research: current and emerging applications.Nature reviews. Endocrinology · 2024Article
- Pituitary stem cells: past, present and future perspectives.Nature reviews. Endocrinology · 2024Review
- Generation and purification of ACTH-secreting hPSC-derived pituitary cells for effective transplantation.Stem cell reports · 2023Article
- c-Jun N-terminal kinase 1 (JNK1) phosphorylates OTX2 transcription factor that regulates early retinal development.Genes & genomics · 2023Article
- iPSC-derived three-dimensional brain organoid models and neurotropic viral infections.Journal of neurovirology · 2023Review
Corrections and comments
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Authors and funding
11 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Pituitary develops from oral ectoderm in contact with adjacent ventral hypothalamus. Impairment in this process results in congenital pituitary hypoplasia (CPH); however, there have been no human disease models for CPH thus far, prohibiting the elucidation of the underlying mechanisms. In this study, we established a disease model of CPH using patient-derived induced pluripotent stem cells (iPSCs) and 3D organoid technique, in which oral ectoderm and hypothalamus develop simultaneously. Interestingly, patient iPSCs with a heterozygous mutation in the orthodenticle homeobox 2 (OTX2) gene showed increased apoptosis in the pituitary progenitor cells, and the differentiation into pituitary hormone-producing cells was severely impaired. As an underlying mechanism, OTX2 in hypothalamus, not in oral ectoderm, was essential for progenitor cell maintenance by regulating LHX3 expression in oral ectoderm via FGF10 expression in the hypothalamus. Convincingly, the phenotype was reversed by the correction of the mutation, and the haploinsufficiency of OTX2 in control iPSCs revealed a similar phenotype, demonstrating that this mutation was responsible. Thus, we established an iPSC-based congenital pituitary disease model, which recapitulated interaction between hypothalamus and oral ectoderm and demonstrated the essential role of hypothalamic OTX2.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.