Single-Nucleus Chromatin Accessibility Landscape Reveals Diversity in Regulatory Regions Across Distinct Adult Rat Cortex.

Yeya Yu,Lei Han,Peng Fan,Shuncheng Shangguan,Qiuting Deng,Miguel A Esteban,Chuanyu Liu,Yiping Guo,Yiwei Lai,Qing Lan,Longqi Liu,Peiying Wu,Yang Liu,Yue Yuan,Xiaoyu Wei,Yong Hou,Giacomo Volpe

doi:10.3389/fnmol.2021.651355

Abstract

Rats have been widely used as an experimental organism in psychological, pharmacological, and behavioral studies by modeling human diseases such as neurological disorders. It is critical to identify and characterize cell fate determinants and their regulatory mechanisms in single-cell resolutions across rat brain regions. Here, we applied droplet-based single-nucleus assay for transposase-accessible chromatin using sequencing (snATAC-seq) to systematically profile the single-cell chromatin accessibility across four dissected brain areas in adult Sprague–Dawley (SD) rats with a total of 59,023 single nuclei and identified 16 distinct cell types. Interestingly, we found that different cortex regions exhibit diversity in both cellular compositions and gene regulatory regions. Several cell-type-specific transcription factors (TFs), including SPI1, KLF4, KLF6, and NEUROD2, have been shown to play important roles during the pathogenesis of various neurological diseases, such as Alzheimer’s disease (AD), astrocytic gliomas, autism spectrum disorder (ASD), and intellectual disabilities. Therefore, our single-nucleus atlas of rat cortex could serve as an invaluable resource for dissecting the regulatory mechanisms underlying diverse cortex cell fates and further revealing the regulatory networks of neuropathogenesis.

Highlights

The rat, one of the most widely used model organisms, is invaluable for biomedical research by modeling human physiology and diseases (Grigorutaet al., 2020; Ma et al, 2020)
We obtained a total of 59,023 cells that passed the quality control (QC) from the rat cortex, creating a new single nucleus database that would serve as a helpful resource for future studies in neurological diseases
The rat was transported by air to the Guangzhou Institute of Biomedicine and Health (GIBH) of the Chinese Academy of Sciences, where GIBH colleagues helped with tissue dissection

Summary

INTRODUCTION

The rat, one of the most widely used model organisms, is invaluable for biomedical research by modeling human physiology and diseases (Grigorutaet al., 2020; Ma et al, 2020). Recent studies have shown that the neurogenesis rate in the hippocampus of adult rats is much greater than that of adult mice, revealing differences in the plasticity of neural cells between rats and mice (Snyder et al, 2009). With the advancement of genetics and genomics technologies, using a rat as an experimental model, several factors have been identified that play critical roles in both brain physiology and disease (Xu et al, 2019; Berg et al, 2020). The cerebral cortex, the brain’s outer layer, is composed of many different regions These regions are involved in complex brain functions that are related to various sensations and movements of the body and to various cognitive abilities such as language and thinking. We obtained a total of 59,023 cells that passed the quality control (QC) from the rat cortex, creating a new single nucleus database that would serve as a helpful resource for future studies in neurological diseases

MATERIALS AND METHODS

AND DISCUSSION

Findings

ETHICS STATEMENT