解码人类海马体的发育

海马体是人脑边缘系统的重要组成部分，在空间导航和从短期记忆到长期记忆的信息整合中具有重要作用1,2。在这里，我们使用单细胞RNA测序和使用测序（ATAC–seq）分析测定转座酶可及染色质，以说明发育中的人类海马的细胞类型、细胞排列、分子特征和转录调节。使用孕16-27周时来自人类海马的30416个细胞的转录组，我们确定了47个细胞亚型及其发育轨迹。我们还确定了PAX6+和HOPX+海马祖细胞的迁移路径和细胞谱系，以及CA1、CA3和齿状回神经元的区域标记。多组数据揭示了齿状回标记物PROX1的转录调控网络。我们还说明了发育中的人类前额叶皮层和海马体中的空间特异性基因表达。妊娠16至20周的人类海马体的分子特征与出生后第0至5天的小鼠相似，并揭示了两个物种之间的基因表达差异。灵长类动物特异性基因NBPF1的瞬时表达导致小鼠海马中PROX1+细胞的显著增加。这些数据为理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 a critical component of the limbic system in the human brain, and plays essential roles in spatial navigation and information integration from short-term to long-term memory1,2. Here, we employed single-cell RNA sequencing and Assay for Transposase-Accessible Chromatin using sequencing (ATAC-seq) to characterize cell types, cellular organization, molecular signatures, and transcriptional regulation in the developing human hippocampus. Using transcriptomic data from 30,416 cells isolated from the human hippocampus at gestational weeks 16–27, we identified 47 cell subtypes and their developmental trajectories. We also characterized the migratory routes and cell lineages of PAX6+ and HOPX+ hippocampal progenitor cells, as well as region-specific markers for CA1, CA3, and dentate gyrus neurons. Multi-omic data revealed the transcriptional regulatory network of PROX1, a marker of the dentate gyrus. We also illustrated spatially specific gene expression in the developing human prefrontal cortex and hippocampus. The molecular signatures of the human hippocampus at gestational weeks 16–20 are similar to those of mice at postnatal days 0–5, and reveal gene expression differences between the two species. Transient expression of the primate-specific gene NBPF1 resulted in a significant increase in PROX1+ cells in the mouse hippocampus. These data provide a blueprint for understanding human hippocampal development and a tool for investigating related neurological disorders.

搜集汇总

背景与挑战

背景概述

该数据集通过单细胞RNA测序和ATAC-seq技术，研究了人类海马体在妊娠16-27周的发育过程，识别出47种细胞亚型及其发育轨迹，揭示了PAX6+和HOPX+海马祖细胞的迁移路径和细胞谱系，以及CA1、CA3和齿状回神经元的区域标记。数据集包含16个样本，总计548.99 GB的测序数据。