Decoding the development of the human hippocampus

• Published in: Nature (London) 2020-01, Vol.577 (7791), p.531-536
• Main Authors: Zhong, Suijuan, Ding, Wenyu, Sun, Le, Lu, Yufeng, Dong, Hao, Fan, Xiaoying, Liu, Zeyuan, Chen, Ruiguo, Zhang, Shu, Ma, Qiang, Tang, Fuchou, Wu, Qian, Wang, Xiaoqun
• Format: Article
• Language: English
• Subjects: 45/91; 631/136/368/2430; 631/378/2571/2578; Animals; Carrier Proteins - metabolism; Cell Lineage; Dentate Gyrus - cytology; Dentate Gyrus - embryology; Dentate Gyrus - metabolism; Evolution, Molecular; Female; Gene Expression Regulation, Developmental - genetics; Genetic aspects; Hippocampus (Brain); Hippocampus - cytology; Hippocampus - embryology; Hippocampus - metabolism; Homeodomain Proteins - metabolism; Humanities and Social Sciences; Humans; Male; Mice; multidisciplinary; Neural Stem Cells - cytology; Neural Stem Cells - metabolism; Neurogenesis; Neurons - cytology; Neurons - metabolism; PAX6 Transcription Factor - metabolism; Physiological aspects; Prefrontal Cortex - cytology; Prefrontal Cortex - embryology; Prefrontal Cortex - metabolism; Science; Science (multidisciplinary); Species Specificity; Transcriptome - genetics; Tumor Suppressor Proteins - metabolism
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/s41586-019-1917-5

The hippocampus is an important part of the limbic system in the human brain that has essential roles in spatial navigation and the consolidation of information from short-term memory to long-term memory 1 , 2 . Here we use single-cell RNA sequencing and assay for transposase-accessible chromatin using sequencing (ATAC–seq) analysis to illustrate the cell types, cell linage, molecular features and transcriptional regulation of the developing human hippocampus. Using the transcriptomes of 30,416 cells from the human hippocampus at gestational weeks 16–27, we identify 47 cell subtypes and their developmental trajectories. We also identify the migrating paths and cell lineages of PAX6 + and HOPX + hippocampal progenitors, and regional markers of CA1, CA3 and dentate gyrus neurons. Multiomic data have uncovered transcriptional regulatory networks of the dentate gyrus marker PROX1. We also illustrate spatially specific gene expression in the developing human prefrontal cortex and hippocampus. The molecular features of the human hippocampus at gestational weeks 16–20 are similar to those of the mouse at postnatal days 0–5 and reveal gene expression differences between the two species. Transient expression of the primate-specific gene NBPF1 leads to a marked increase in PROX1 + cells in the mouse hippocampus. These data provides a blueprint for understanding human hippocampal development and a tool for investigating related diseases. Single-cell RNA sequencing is used to catalogue and explore the developmental trajectories of more than 30,000 cells in the developing human hippocampus.