Dynamic Changes of Brain Cilia Transcriptomes across the Human Lifespan.

Area of Science:

• Neuroscience
• Cell Biology
• Genetics

Background:

• Primary cilia are crucial microtubule-based sensory organelles found on nearly all brain cells.
• Cilia play vital roles in neurodevelopment, brain maturation, and adult brain signaling.
• Cilia structure and function likely change across the human lifespan, influencing brain physiology.

Purpose of the Study:

• To investigate age-dependent expression patterns of cilia's structural and functional components in the human brain.
• To identify brain regions with significant age-related changes in cilia gene expression.
• To explore the implications of these changes for normal brain function and age-related disorders.

Main Methods:

• Acquired cilia transcriptomic data from 16 human brain regions using the BrainSpan Atlas.
• Analyzed age-dependent expression patterns using linear regression and calculated regression coefficients.
• Identified differentially expressed genes with age (DEGAs) in cilia transcripts.

Main Results:

• 67% of cilia transcripts were DEGAs in at least one brain region, with region-specific patterns.
• Most DEGAs were upregulated with age, particularly basal body components, with notable exceptions like specific tubulin subunits and SNAP-25.
• Specific tubulin subunits (TUBA1A, TUBB2A, TUBB2B) downregulated, while SNAP-25 upregulated across most brain regions with age.

Conclusions:

• Significant age-dependent dynamics exist in cilia structural and functional components across the human lifespan.
• These dynamics are crucial for normal brain circuit physiology.
• Cilia signaling may play a key role in the pathophysiology of age-related neurological and psychiatric disorders.