Publications by authors named "P Paddison"
Glioblastoma (GBM) is the most common and aggressive brain tumor in adults. To identify genes differentially required for the viability of GBM stem-like cells (GSCs), we performed functional genomic lethality screens comparing GSCs and control human neural stem cells. Among top-scoring hits in a subset of GBM cells was the F-box-containing gene , which was also predicted to be essential in ∼15% of cell lines derived from a broad range of cancers.
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- Single-cell transcriptomics reveals diverse cellular behavior, with a focus on the importance of cell cycle stages in human neural stem cells.
- The ccAFv2 classifier categorizes cells into six distinct cell cycle states and a quiescent-like state, outperforming existing methods while offering flexibility and customizable classifications.
- Demonstrated effectiveness across different cell types and species, ccAFv2 is accessible as an R package and a Python package, making it a valuable resource for analyzing complex biological data and understanding cellular dynamics.
Article Synopsis
- Glioblastoma is a highly fatal brain tumor with chromosomal alterations affecting oncogenes and tumor suppressors, and research identified 6q27 as a poor prognostic marker.
- Using a combination of CRISPR, transcriptomic data, and mouse models, the study explored Pde10a as a potential tumor suppressor in the 6q27 region and found its suppression leads to aggressive tumor behavior and treatment resistance.
- Pde10a suppression was linked to enhanced PI3K/AKT signaling and a change in tumor cell characteristics, suggesting glioblastoma patients with Pde10a loss may have worse outcomes but might benefit from PI3K inhibitors.
3' untranslated region (3' UTR) somatic mutations represent a largely unexplored avenue of alternative oncogenic gene dysregulation. To determine the significance of 3' UTR mutations in disease, we identify 3' UTR somatic variants across 185 advanced prostate tumors, discovering 14,497 single-nucleotide mutations enriched in oncogenic pathways and 3' UTR regulatory elements. By developing two complementary massively parallel reporter assays, we measure how thousands of patient-based mutations affect mRNA translation and stability and identify hundreds of functional variants that allow us to define determinants of mutation significance.
View Article and Find Full Text PDFHuman CD34+ hematopoietic stem and progenitor cells (HSPCs) are a standard source of cells for clinical HSC transplantations as well as experimental xenotransplantation to generate "humanized mice". To further extend the range of applications of these humanized mice, we developed a protocol to efficiently edit the genomes of human CD34+ HSPCs before transplantation. In the past, manipulating HSPCs has been complicated by the fact that they are inherently difficult to transduce with lentivectors, and rapidly lose their stemness and engraftment potential during in vitro culture.
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