A5093246200- Neuroblastoma Research and Treatments
- Immune cells in cancer
- Glioma Diagnosis and Treatment
- Neuroinflammation and Neurodegeneration Mechanisms
- Extracellular vesicles in disease
- Hippo pathway signaling and YAP/TAZ
- Cancer, Hypoxia, and Metabolism
- Immune Cell Function and Interaction
- Fibroblast Growth Factor Research
McGill University
2023-2024
<p>Bulk RNAseq projections by ssGSEA.</p>
<p>Orthotopic engraftment of cell lines derived from Foxr2 p53LOF murine model.</p>
<p><i>Foxr2</i> is oncogenic in the ventral telencephalon mice. <b>A,</b> Schematic describing IUE-based strategy to model <i>FOXR2</i>-driven brain tumors. PiggyBac and CRISPR vectors are delivered into neural stem cells GEs at E12.5. After birth, mice develop tumors euthanized when neurologic symptoms become apparent. <b>B,</b> Representative brightfield (BF) fluorescence (GFP) images of a GFP+ <i>Foxr2</i>-driven tumor...
<p>Foxr2 chromatin binding sites in <i>Foxr2</i> p53<sup>LOF</sup> neurosphere show enrichment ETS and glial pathways. <b>A,</b> Validation of FOXR2 overexpression p53 downregulation <i>ex vivo</i><i>Foxr2</i> neurospheres by qRT-PCR. <b>B,</b> <i>Nkx2-1</i>, <i>Lhx6</i>, <i>Dlx5</i>, <i>Dlx6</i>, <i>Emx2</i>, <i>Sox10</i>,...
<p><i>FOXR2</i> does not induce expression of MGE or EC-NB TFs. <b>A,</b> Bulk RNA-seq telencephalon patterning Top and third rows, tumor samples from this study cohort. Second row, (Gartlgruber colleagues, ref. <a href="#bib21" target="_blank">21</a>) subset to high risk, stage 4 with <i>FOXR2</i> (normalized >2). Bottom H9 human NSCs transduced HA-FOXR2 controls HcRed (Tsai href="#bib7" target="_blank">7</a>). All box plots...
<p>Mouse models transcriptomically recapitulate human NB-FOXR2. <b>A,</b> Heatmap showing CNVs in <i>Foxr2</i> p53<sup>LOF</sup> and alone models, computed with inferCNV. <b>B,</b> Top, Uniform Manifold Approximation Projection (UMAP) joint representation of mouse model single-cell datasets (<i>n</i> = 3) without integration or batch correction. Cells colored by broad cell class derived from automated type annotation,...
<p>NB-FOXR2 tumors transcriptionally resemble interneurons and OPC cells. <b>A,</b><i>t</i>-Distributed stochastic neighbor embedding (<i>t</i>-SNE) of bulk RNA-seq profiles pediatric brain (left) with stage 4 high-risk EC-NBs from Gartlgruber colleagues (ref. <a href="#bib21" target="_blank">21</a>; right) using ssGSEA scores for <i>N</i> = 374 cell type–specific gene signatures reference scRNA-seq datasets....
<p>Quality control (QC) metrics and copy-number variation for scRNAseq datasets of NB-FOXR2 patient tumors.</p>
<p>NB-FOXR2 express a transcription factor fingerprint of the medial ganglionic eminence.</p>
<p>Transcription factor (TF) patterning in normal reference datasets.</p>
<p>Mouse models transcriptomically recapitulate human NB-FOXR2</p>
<p>NB-FOXR2 tumors transcriptionally resemble interneurons and oligodendrocyte precursor cells.</p>
<p>NB-FOXR2 expresses a TF fingerprint of the MGE. <b>A,</b> Expression telencephalon-patterning TFs in embryonal mouse brain. Top, stereo-seq <i>in situ</i> RNA expression E14 (Chen and colleagues, ref. <a href="#bib75" target="_blank">75</a>; href="https://db.cngb.org/stomics/mosta/spatial/" target="_blank">https://db.cngb.org/stomics/mosta/spatial/</a>). Middle, hybridization E13 (Allen Brain Atlas,...
<div>Abstract<p>Central nervous system neuroblastoma with <i>forkhead box R2</i> (<i>FOXR2</i>) activation (NB-FOXR2) is a high-grade tumor of the brain hemispheres and newly identified molecular entity. Tumors express dual neuronal glial markers, leading to frequent misdiagnoses, limited information exists on role <i>FOXR2</i> in their genesis. To identify cellular origins, we profiled transcriptomes NB-FOXR2 tumors at bulk single-cell levels...