ArticleStem cell reports2023
Organoid models of breathing disorders reveal patterning defect of hindbrain neurons caused by PHOX2B-PARMs.
Article in Stem cell reports, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 1 of them a synthesis that pooled it.
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Who cites it
10 citing papers in PubMed, 1 synthesis or guideline pooled it, 11 citations in OpenAlex.
- Mapping the Cerebral Organoid Landscape: A Systematic Review of Preclinical 3D Models in Neuroscience.Advanced healthcare materials · 2026Pooled it
- Single-cell multi-omic atlas and morphogen screening informs midbrain and hindbrain organoid engineering.Nature neuroscience · 2026Article
- PHOX2B defects alter protein folding, cell-cycle, and mitochondrial pathways in an in vitro model of CCHS.Molecular medicine (Cambridge, Mass.) · 2026Article
- Organoids in Genetic Disorders: from Disease Modeling to Translational Applications.Stem cell reviews and reports · 2025Review
- Retrotrapezoid nucleus chemoreception: mechanisms of function and contributions to disordered breathing in disease.Trends in neurosciences · 2025Review
- Brain organoids: building higher-order complexity and neural circuitry models.Trends in biotechnology · 2025Review
- Biomedical applications of organoids in genetic diseases.Medical review (2021) · 2025Review
- Identification of a histone deacetylase inhibitor as a therapeutic candidate for congenital central hypoventilation syndrome.Molecular therapy. Nucleic acids · 2024Article
- Comprehensive Gene Expression Analysis Using Human Induced Pluripotent Stem Cells Derived from Patients with Sleep Bruxism: A Preliminary In Vitro Study.International journal of molecular sciences · 2024Article
- Advances in physiological and clinical relevance of hiPSC-derived brain models for precision medicine pipelines.Frontiers in cellular neuroscience · 2024Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Retrotrapezoid nucleus (RTN) neurons in the brainstem regulate the ventilatory response to hypercarbia. It is unclear how PHOX2B-polyalanine repeat mutations (PHOX2B-PARMs) alter the function of PHOX2B and perturb the formation of RTN neurons. Here, we generated human brainstem organoids (HBSOs) with RTN-like neurons from human pluripotent stem cells. Single-cell transcriptomics revealed that expression of PHOX2B+7Ala PARM alters the differentiation trajectories of the hindbrain neurons and hampers the formation of the RTN-like neurons in HBSOs. With the unguided cerebral organoids (HCOs), PHOX2B+7Ala PARM interrupted the patterning of PHOX2B+ neurons with dysregulation of Hedgehog pathway and HOX genes. With complementary use of HBSOs and HCOs with a patient and two mutant induced pluripotent stem cell lines carrying different polyalanine repetition in PHOX2B, we further defined the association between the length of polyalanine repetition and malformation of RTN-respiratory center and demonstrated the potential toxic gain of function of PHOX2B-PARMs, highlighting the uniqueness of these organoid models for disease modeling.
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