Decoding the development of the human hippocampus

Suijuan Zhong, Wenyu Ding, Le Sun, Yufeng Lu, Hao Dong, Xiaoying Fan, Zeyuan Liu, Ruiguo Chen, Shu Zhang, Qiang Ma, Fuchou Tang, Qian Wu () and Xiaoqun Wang ()
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Suijuan Zhong: Chinese Academy of Sciences
Wenyu Ding: Beijing Normal University
Le Sun: Chinese Academy of Sciences
Yufeng Lu: Chinese Academy of Sciences
Hao Dong: Chinese Academy of Sciences
Xiaoying Fan: Peking University
Zeyuan Liu: Chinese Academy of Sciences
Ruiguo Chen: Chinese Academy of Sciences
Shu Zhang: Peking University
Qiang Ma: Chinese Academy of Sciences
Fuchou Tang: Peking University
Qian Wu: Beijing Normal University
Xiaoqun Wang: Chinese Academy of Sciences

Nature, 2020, vol. 577, issue 7791, 531-536

Abstract: Abstract 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 memory1,2. 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.

Date: 2020
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DOI: 10.1038/s41586-019-1917-5

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