Decoding the development of the human hippocampus
Decoding the development of the human hippocampus
复制标题
解码人类海马体的发育
DOI：
10.1038/s41586-019-1917-5
复制
发表时间：
2020-01-01
期刊：
影响因子：
64.8
通讯作者：
Wang, Xiaoqun
中科院分区：
文献类型：
--
作者：
Zhong, Suijuan;Ding, Wenyu;Wang, Xiaoqun
海马体是人脑边缘系统的重要组成部分，在空间导航和短期记忆到长期记忆的信息巩固中起着至关重要的作用。在这里，我们使用单细胞RNA测序和转座酶可及染色质测序（ATAC-seq）分析来阐明发育中的人类海马的细胞类型、细胞谱系、分子特征和转录调控。利用妊娠16-27周人类海马30,416个细胞的转录组，我们鉴定了47个细胞亚型及其发育轨迹。我们还鉴定了PAX6+和HOPX+海马祖细胞的迁移路径和细胞系，以及CA1、CA3和齿状回神经元的区域标记物。多组学数据揭示了齿状回标记物PROX1的转录调控网络。我们还说明了在发育中的人类前额皮质和海马体中空间特异性基因表达。人类海马在妊娠16-20周的分子特征与小鼠出生后0-5天的分子特征相似，揭示了两种动物之间基因表达的差异。灵长类动物特异性基因enbpf1的短暂表达导致小鼠海马中PROX1+细胞的显著增加。这些数据为了解人类海马发育提供了蓝图，也为研究相关疾病提供了工具。
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,. 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 geneNBPF1leads 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.