Dissecting transcriptomic signatures of neuronal differentiation and maturation using iPSCs.

Area of Science:

• Stem cell biology
• Neuroscience
• Transcriptomics
• Developmental biology

Background:

• Human induced pluripotent stem cells (hiPSCs) are crucial for modeling human neural development.
• Understanding the transcriptomic landscape of corticogenesis in hiPSCs is essential for regenerative medicine and disease modeling.

Purpose of the Study:

• To create a comprehensive hiPSC transcriptomics resource for human corticogenesis.
• To investigate transcriptional changes during neural differentiation and maturation.
• To develop methods for assessing neuronal maturity in vitro and in vivo.

Main Methods:

• Generation of hiPSC lines from multiple donors and subclones.
• Transcriptomic profiling across various developmental stages (self-renewal, NPCs, differentiated neurons).
• Co-culture experiments with rodent astrocytes.
• Adaptation of RNA deconvolution for single-cell expression data analysis.

Main Results:

• Identification of widespread changes in gene expression patterns during hiPSC-derived corticogenesis.
• Demonstration of synergistic maturation through co-culturing with rodent astrocytes.
• Extraction of cell type-specific expression data without cell sorting.
• Neuronal cultures exhibit maturational heterogeneity, with some subsets showing advanced maturation.

Conclusions:

• The hiPSC transcriptomics resource provides valuable insights into human corticogenesis.
• Co-culturing with astrocytes enhances neuronal maturation.
• Advanced computational methods enable robust assessment of neuronal maturity in iPSC-derived cultures and human brain tissue.