Modeling striatal development and disease with human pluripotent stem cells - PubMed
3 hours ago
- #striatum
- #medium spiny neurons
- #pluripotent stem cells
- The striatum is crucial for motor control, cognition, reward processing, and habit formation, with dysfunction linked to neurological and psychiatric disorders.
- Human pluripotent stem cells (PSCs) offer a valuable platform for modeling human striatal development and disease, overcoming limitations of animal models due to species-specific differences.
- Current approaches focus on generating medium spiny neurons (MSNs) from PSCs, emphasizing dorsal and ventral striatal specification and the protracted maturation of human MSNs.
- Advances in differentiation strategies, including small molecule patterning, transcription factor induction, and 3D organoid/assembloid systems, enhance model efficiency and complexity.
- PSC-derived striatal models are primarily used in Huntington's disease research, revealing early developmental, transcriptional, synaptic, and network abnormalities.
- Recent studies extend these models to other neurological conditions and incorporate circuit-level analyses using cortico-striatal assembloids.
- Single-cell and single-nucleus transcriptomic datasets provide reference frameworks for benchmarking PSC-derived striatal cell identity and maturation.
- Current challenges include incomplete maturation, limited non-neuronal cell representation, and restricted applicability to psychiatric disorders.
- Future directions involve integrating developmental biology, multi-omics resources, and advanced in vitro strategies to improve models for translational neuroscience.