Publications by authors named "Flavia Peci"
Detection of somatic mutations in single cells has been severely hampered by technical limitations of whole-genome amplification. Novel technologies including primary template-directed amplification (PTA) significantly improved the accuracy of single-cell whole-genome sequencing (WGS) but still generate hundreds of artifacts per amplification reaction. We developed a comprehensive bioinformatic workflow, called the PTA Analysis Toolbox (PTATO), to accurately detect single base substitutions, insertions-deletions (indels), and structural variants in PTA-based WGS data.
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- - The study explores the use of advanced CRISPR/Cas9-based base editors for creating intricate tumor models using human organoids derived from adult stem cells (ASC), specifically focusing on liver (hepatocyte) and endometrial organoids.
- - Results demonstrate the effectiveness of cytosine and adenine base editors in inducing specific mutations, such as CTNNB1 mutations in liver organoids and PTEN nonsense mutations in endometrial organoids, which lead to tumor development even with one mutated copy.
- - Additionally, the researchers enhanced base editing capabilities by employing multiple Cas9 variants for targeted mutations and established a method to model colorectal cancer by editing five cancer genes simultaneously in one experiment.
Allogeneic hematopoietic cell transplantation (HCT) is a potentially curative therapy for patients with a variety of malignant and non-malignant diseases. Despite its life-saving potential, HCT is associated with significant morbidity and mortality. Reciprocal interactions between hematopoietic stem cells (HSCs) and their surrounding bone marrow (BM) niche regulate HSC function during homeostatic hematopoiesis as well as regeneration.
View Article and Find Full Text PDFMutational signatures have been identified in cancer genomes, providing information about the causes of cancer and treatment vulnerabilities. This protocol describes an assay to determine the genotoxic mechanisms underlying these signatures using cord-blood derived hematopoietic stem and progenitor cells (CB-HSPCs). CB-HSPCs have a low mutation background, enabling sensitive detection of mutations.
View Article and Find Full Text PDFGenetic instability is a major concern for successful application of stem cells in regenerative medicine. However, the mutational consequences of the most applied stem cell therapy in humans, hematopoietic stem cell transplantation (HSCT), remain unknown. Here we characterized the mutation burden of hematopoietic stem and progenitor cells (HSPCs) of human HSCT recipients and their donors using whole-genome sequencing.
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