Human Pituitary Organoids: Transcriptional Landscape Deciphered by scRNA-Seq and Stereo-Seq, with Insights into SOX3's Role in Pituitary Development.

Summary

This study optimized human pituitary organoid culture, then applied scRNA-seq and Stereo-seq to map cell types, interactions, and spatial organization. SOX3 knockdown impeded iPSC differentiation into pituitary organoids, nominating SOX3 as a key developmental regulator. The work delivers both an improved protocol and a foundational multi-omic dataset for pituitary disease modeling.

Key Findings

• Optimized differentiation conditions increased iPSC-to-pituitary organoid efficiency to meet or exceed prior studies.
• First application of scRNA-seq and Stereo-seq to human pituitary organoids defined diverse cell clusters, intercellular signaling, and spatial architecture.
• SOX3 gene interference impaired organoid differentiation, indicating a required role in pituitary development.

Clinical Implications

While preclinical, the platform can model hypopituitarism, pituitary tumors, and test genotype-phenotype relationships or drug responses in a human context.

Limitations

• Preclinical organoid model lacks full vascularization and systemic endocrine feedback
• Quantitative functional hormone secretion and long-term maturation were not detailed

Future Directions

Integrate vascular/endothelial components and assess endocrine functionality; leverage the dataset to model genetic pituitary disorders and test therapeutics.