0000000000033389
AUTHOR
Ashley M. Laughney
High resolution mouse subventricular zone stem cell niche transcriptome reveals features of lineage, anatomy, and aging
AbstractAdult neural stem cells (NSC) serve as a reservoir for brain plasticity and origin for certain gliomas. Lineage tracing and genomic approaches have portrayed complex underlying heterogeneity within the major anatomical location for NSC, the subventricular zone (SVZ). To gain a comprehensive profile of NSC heterogeneity, we utilized a well validated stem/progenitor specific reporter transgene in concert with single cell RNA sequencing to achieve unbiased analysis of SVZ cells from infancy to advanced age. The magnitude and high specificity of the resulting transcriptional data sets allow precise identification of the varied cell types embedded in the SVZ including specialized parench…
High-resolution mouse subventricular zone stem-cell niche transcriptome reveals features of lineage, anatomy, and aging
Adult neural stem cells (NSC) serve as a reservoir for brain plasticity and origin for certain gliomas. Lineage tracing and genomic approaches have portrayed complex underlying heterogeneity within the major anatomical location for NSC, the subventricular zone (SVZ). To gain a comprehensive profile of NSC heterogeneity, we utilized a well-validated stem/progenitor-specific reporter transgene in concert with single-cell RNA sequencing to achieve unbiased analysis of SVZ cells from infancy to advanced age. The magnitude and high specificity of the resulting transcriptional datasets allow precise identification of the varied cell types embedded in the SVZ including specialized parenchymal cell…
TMOD-36. PRECISE INVESTIGATION OF CANCER STEM CELLS IN A MOUSE GLIOBLASTOMA MODEL
Cancer stem cells (CSCs) have been shown to play a critical role in glioblastoma (GBM) pathogenesis. However, a precise and thorough understanding of these cells is still lacking. Here we design a novel mouse model to label, purify, and study cancer stem cells in vivo. Firstly we generate and characterize a new transgene to label neural stem/progenitor cells in the subventricular zone (SVZ) with GFP, and drive expression of CreERT2 and human diphtheria toxin receptor in the same cells (CGD: nestin-CreERT2-H2BeGFP-hDTR). Following analysis with both bulk and single cell RNA sequencing of the SVZ tissue demonstrate its faithful expression in the stem/progenitor cell compartment. We then cross…
Abstract 3015: Precise investigation of cancer stem cells in mouse glioblastoma
Abstract In this study, we employ mouse models to investigate features and roles of cancer stem cells (CSCs) in glioblastoma (GBM). A nestin-TK-GFP transgene is firstly used to label CSCs in a fully penetrant mouse model of GBM (M7: hGFAP-Cre; Nf1fl/+; p53fl/fl; Ptenfl/+). Food-mediated ganciclovir (GCV) delivery kills proliferative transgene positive cells and significantly prolongs the lives of the transgene bearing mice. Isolation and transplantation of the tumor cells indicates the GFP+ cells are more tumorigenic than the GFP- cells. We then generate and characterize a novel transgene (CGD: nestin-CreERT2-H2BeGFP-hDTR) that labels all the neural stem/progenitor cells in the subventricul…