Fusion transcripts in normal human cortex increase with age and show distinct genomic features for single cells and...

Area of Science:

• Neuroscience
• Genomics
• Molecular Biology

Background:

• Fusion transcripts can diversify molecular networks in the human brain.
• Their role in normal human cortex, neurons, and astrocytes requires further exploration.

Purpose of the Study:

• To investigate the occurrence and characteristics of fusion transcripts in the human cortex.
• To compare fusion events in whole cortex, single neurons, and astrocytes.
• To explore the relationship between fusion transcripts, age, and brain function.

Main Methods:

• Analysis of 388 transcriptomes from 59 human cortices and 329 single cells.
• Identification and classification of fusion events (intra- vs. inter-chromosomal).
• Comparison of fusion transcript numbers and types across cell types and age groups.

Main Results:

• Identified 1305 non-redundant fusion events.
• Intra-chromosomal fusions dominate the cortex (85%), while inter-chromosomal fusions are prevalent in single cells (80%).
• Fusion transcript numbers increase with age and differ between fetal and adult brain pathways (LTD vs. LTP).

Conclusions:

• Fusion transcripts are a natural phenomenon in the human brain, contributing to molecular diversity.
• Their prevalence and type vary between cell types and with age.
• Fusion transcripts may play a role in brain plasticity and span the health-disease continuum.