The brain is the most complex organ in the human body, and its complexity is far beyond our current knowledge. And the prefrontal cortex is a key component of human brain's advanced functions, which is involved in memory formation, short-term storage, retrieval function, language function, emotion regulation and other functions. To understand how the human brain works, a necessary foundation is a detailed and accurate "cell type map" of the human brain. Up to now, we know little about the cell types in the prefrontal cortex of the human brain and how these cells are produced during embryonic development.

In 14^th, Mar 2018, Fuchou Tang research group of Beijing Advanced Innovation Center for Genomics published online a letter paper named 'Single-cell RNA-Seq surveys a developmental landscape of the human prefrontal cortex' with collaborators. In the study, the researchers utilized single cell RNA-seq analysis to draw the single cell transcriptome map of developing human prefrontal cortex, uncovered the cell type diversities and molecular regulations of regarding the neurogenesis process and further characterized the functions of important cell types. This work laid a foundation in plotting the whole cellular map of human brain.

In the study, the researchers identified the human specific neurogenesis pattern that there were two peaks of intermediate progenitor cells (IPCs) generation at GW10 and GW16. The IPCs differentiated from radial glia (RG) cells at GW10 while differentiated from oRG cells at GW16. The two boosts of IPCs are important for the generation of large abundance of neurons in a short time and finally formed the complex structures of prefrontal cortex.

Moreover, the researchers identified the key periods for neural developmental events: GW8-GW12 is the key period for expansion of neural stem cells, GW13-GW16 enriched with the neural differentiation and migration, during GW19-GW26 neurons became mature and initially formed neural networks.

Finally, to uncover the genesis of inhibitory neurons, the researchers find that a small number of inhibitory neuron precursors existed in the early stage of prefrontal cortex using single-cell transcriptome sequencing and immunostaining. But most of the precursors were in the quiescent state of the cell cycle, and may not divide and generate neurons temporarily. What’s more, transcriptome data analysis also showed that the maturation of excitatory neurons in the prefrontal cortex was earlier than that of inhibitory neurons.

The cell composition of prefrontal cortex is the biological basis for the formation of neural networks and complex functions of brain. Through high-resolution single cell transcriptome sequencing and systematic bioinformatics analysis, our study accurately explored and analyzed the cellular and molecular mechanisms of human prefrontal cortex development, which provides a critical resource for understanding the development of human prefrontal cortex.

The diagram of the development of human fetal prefrontal cortex

Two key peaks of IPCs proliferation in prefrontal cortex

The development timeline of human prefrontal cortex cells appearance, differentiation and functional generation