Transcriptome Response and Spatial Pattern of Gene Expression in the Primate Subventricular Zone Neurogenic Niche After Cerebral Ischemia.

Monika C Chongtham,Gregor Eichele,Tetsumori Yamashima,Stoyan P Pavlov,Lorenz H Williamson,Christina Thaller,Ivan H Vachkov,Nai-Hua Hsiao,Anton B Tonchev,Jun Yan,Haifang Wang,Anastassia Stoykova

doi:10.3389/fcell.2020.584314

Abstract

The main stem cell niche for neurogenesis in the adult mammalian brain is the subventricular zone (SVZ) that extends along the cerebral lateral ventricles. We aimed at characterizing the initial molecular responses of the macaque monkey SVZ to transient, global cerebral ischemia. We microdissected tissue lining the anterior horn of the lateral ventricle (SVZa) from 7 day post-ischemic and sham-operated monkeys. Transcriptomics shows that in ischemic SVZa, 541 genes were upregulated and 488 genes were down-regulated. The transcription data encompassing the upregulated genes revealed a profile typical for quiescent stem cells and astrocytes. In the primate brain the SVZ is morphologically subdivided in distinct and separate ependymal and subependymal regions. The subependymal contains predominantly neural stem cells (NSC) and differentiated progenitors. To determine in which SVZa region ischemia had evoked transcriptional upregulation, sections through control and ischemic SVZa were analyzed by high-throughput in situ hybridization for a total of 150 upregulated genes shown in the www.monkey-niche.org image database. The majority of the differentially expressed genes mapped to the subependymal layers on the striatal or callosal aspect of the SVZa. Moreover, a substantial number of upregulated genes was expressed in the ependymal layer, implicating a contribution of the ependyma to stem cell biology. The transcriptome analysis yielded several novel gene markers for primate SVZa including the apelin receptor that is strongly expressed in the primate SVZa niche upon ischemic insult.

Highlights

Neurogenesis in the adult mammalian brain takes place in two niches, the subventricular zone (SVZa) lining the anterior horn of the forebrain lateral ventricle and the subgranular zone (SGZ) of the dentate gyrus
We found that ischemic SVZa shows a transcriptional profile reminiscent of a profile typical for quiescent stem cells, astrocytes and oligodendrocytes
To uncover the changes in gene expression upon ischemia in the macaque SVZa niche, we performed transient global cerebral ischemia in adult macaque monkeys. In both sham-operated and ischemic tissue ∼25,000 transcripts corresponding to ∼16,000 genes were detected (Supplementary Table S2)

Summary

INTRODUCTION

Neurogenesis in the adult mammalian brain takes place in two niches, the subventricular zone (SVZa) lining the anterior horn of the forebrain lateral ventricle and the subgranular zone (SGZ) of the dentate gyrus In these microenvironments, astrocytelike neural stem cells (NSCs) proliferate and produce neural precursors generating neuronal and glial progeny (Obernier and Alvarez-Buylla, 2019). We have previously established a model of transient global ischemia in adult macaque monkey Such ischemia induces regional tissue damage affecting neuronal populations in the hippocampus, striatum, neocortex and cerebellum (Yamashima et al, 1996; Yoshida et al, 2002). A comparative analysis of the expression pattern these 150 genes yielded several novel gene markers for SVZa cells, including the apelin receptor (APLNR)

MATERIALS AND METHODS

Surgical Procedures and SVZa Microdissection

RESULTS

DISCUSSION

DATA AVAILABILITY STATEMENT