0000000000033393
AUTHOR
Olivier Elemento
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…
EZH2 mutations are frequent and represent an early event in follicular lymphoma
Gain of function mutations in the H3K27 methyltransferase EZH2 represent a promising therapeutic target in germinal center lymphomas. In this study, we assessed the frequency and distribution of EZH2 mutations in a large cohort of patients with follicular lymphoma (FL) (n = 366) and performed a longitudinal analysis of mutation during the disease progression from FL to transformed FL (tFL) (n = 33). Mutations were detected at 3 recurrent mutation hot spots (Y646, A682, and A692) in 27% of FL cases with variant allele frequencies (VAF) ranging from 2% to 61%. By comparing VAF of EZH2 with other mutation targets (CREBBP, MLL2, TNFRSF14, and MEF2B), we were able to distinguish patients harbori…
Deep learning enables robust assessment and selection of human blastocysts after in vitro fertilization
AbstractVisual morphology assessment is routinely used for evaluating of embryo quality and selecting human blastocysts for transfer after in vitro fertilization (IVF). However, the assessment produces different results between embryologists and as a result, the success rate of IVF remains low. To overcome uncertainties in embryo quality, multiple embryos are often implanted resulting in undesired multiple pregnancies and complications. Unlike in other imaging fields, human embryology and IVF have not yet leveraged artificial intelligence (AI) for unbiased, automated embryo assessment. We postulated that an AI approach trained on thousands of embryos can reliably predict embryo quality with…
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…
Robust Automated Assessment of Human Blastocyst Quality using Deep Learning
AbstractMorphology assessment has become the standard method for evaluation of embryo quality and selecting human blastocysts for transfer inin vitro fertilization(IVF). This process is highly subjective for some embryos and thus prone to human bias. As a result, morphological assessment results may vary extensively between embryologists and in some cases may fail to accurately predict embryo implantation and live birth potential. Here we postulated that an artificial intelligence (AI) approach trained on thousands of embryos can reliably predict embryo quality without human intervention.To test this hypothesis, we implemented an AI approach based on deep neural networks (DNNs). Our approac…