Conserved properties of dentate gyrus neurogenesis across postnatal development revealed by single-cell RNA sequencing.

Hannah Hochgerner,Sten Linnarsson,Amit Zeisel,Peter Lönnerberg

doi:10.1038/s41593-017-0056-2

Hannah Hochgerner, Sten Linnarsson + Show 2 more

Open Access

https://doi.org/10.1038/s41593-017-0056-2

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Abstract

The dentate gyrus of the hippocampus is a brain region in which neurogenesis persists into adulthood; however, the relationship between developmental and adult dentate gyrus neurogenesis has not been examined in detail. Here we used single-cell RNA sequencing to reveal the molecular dynamics and diversity of dentate gyrus cell types in perinatal, juvenile, and adult mice. We found distinct quiescent and proliferating progenitor cell types, linked by transient intermediate states to neuroblast stages and fully mature granule cells. We observed shifts in the molecular identity of quiescent and proliferating radial glia and granule cells during the postnatal period that were then maintained through adult stages. In contrast, intermediate progenitor cells, neuroblasts, and immature granule cells were nearly indistinguishable at all ages. These findings demonstrate the fundamental similarity of postnatal and adult neurogenesis in the hippocampus and pinpoint the early postnatal transformation of radial glia from embryonic progenitors to adult quiescent stem cells.

Highlights

The dentate gyrus, part of the hippocampus, is involved in learning, episodic memory formation and spatial coding
We provide an online browsable resource where gene expression can be visualized in individual cells and clusters of all three datasets
We have described the perinatal development and persistent adult neurogenesis of the dentate gyrus using single-cell RNA-seq

Summary

Introduction

The dentate gyrus, part of the hippocampus, is involved in learning, episodic memory formation and spatial coding It receives unidirectional input from the entorhinal cortex through the perforant path and projects to the CA3, forming the first step of the hippocampal trisynaptic circuit. The granule layer creates the characteristic V-shape in coronal and most sagittal hippocampus sections. It is densely packed with uniform, small granule cells whose dendrites extend into the overlying molecular layer, receiving input from the entorhinal cortex. A small number of interneurons are present, and the hilus contains a second type of principal excitatory neurons resembling CA3 pyramidal cells, called mossy cells. A variety of GABAergic interneurons have been described, such as the pyramidal basket cell, enriched at the interface of the granule layer to the hilus, known as the subgranular zone, which provide inhibitory control of granule cell activity (schematic Fig. 1e, reviewed in (Amaral et al 2007))

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