Identification and characterization of functional modules reflecting transcriptome transition during human neuron maturation

Zhisong He, Qianhui Yu

Neuron maturation is a critical process in neurogenesis, during which neurons gain their morphological, electrophysiological and molecular characteristics for their functions as the central components of the nervous system. To better understand the molecular changes during this process, we combined the protein-protein interaction network and public single cell RNA-seq data of mature and immature neurons to identify functional modules relevant to the neuron maturation process in humans. Among the 109 functional modules in total, 33 showed significant gene expression level changes (discriminating modules) which participate in varied functions including energy consumption, synaptic functions and housekeeping functions such as translation and splicing. Based on the identified modules, we trained a neuron maturity index (NMI) model for the quantification of maturation states of single neurons or purified bulk neurons. Applied to multiple single neuron transcriptome data sets of neuron development in humans and mice, the NMI model made estimation of neuron maturity states which were significantly correlated with the neuron maturation trajectories in both species, implying the reproducibility and conservation of the identified transcriptome transition. We identified 33 discriminating modules whose activities were significantly correlated with single neuron maturity states, which may play important roles in the neuron maturation process.