CORTECON: a temporal transcriptome analysis of in vitro human cerebral cortex development from human embryonic stem...

Area of Science:

• Neuroscience
• Developmental Biology
• Genetics

Background:

• Neurological and psychiatric disorders impact the cerebral cortex, necessitating a deeper understanding of human corticogenesis.
• Current knowledge of gene expression during corticogenesis relies heavily on murine models, highlighting a need for human-specific data.

Purpose of the Study:

• To create a comprehensive, searchable dataset of temporal gene expression during human corticogenesis using human embryonic stem cells (hESCs).
• To identify genes and long noncoding RNAs (lncRNAs) with significant expression changes during corticogenesis and those associated with diseases.
• To analyze alternative splicing events during human cortical development.

Main Methods:

• Utilized a modified differentiation protocol to generate neurons resembling prefrontal cortex from hESCs.
• Performed comprehensive temporal gene expression profiling, including RNA sequencing.
• Developed an online database (Cortecon) for query-based access to the expression data.

Main Results:

• Generated a detailed temporal gene expression dataset for human cortical development.
• Identified numerous genes and lncRNAs with significant expression changes and disease associations.
• Discovered alternatively spliced genes, such as TGIF1 (holoprosencephaly) and MARK1 (autism), with distinct temporal expression patterns.

Conclusions:

• The developed dataset and database provide valuable resources for studying human corticogenesis and its associated disorders.
• The findings highlight the importance of human-specific gene expression data in understanding neurological and psychiatric conditions.
• The identification of disease-associated genes and alternative splicing events offers potential targets for future research and therapeutic strategies.