Biology subjects

Carli, C.

Publications and source records attributed to Carli, C..

3 recordsLinked to original sources

bioRxiv2026

A first pangenomic framework for globe artichoke supports SNP-based varietal fingerprinting

Globe artichoke (Cynara cardunculus var. scolymus L.) comprises a broad range of local ecotypes and varietal groups whose genetic diversity has been investigated through different molecular markers. However, recent advances in next-generation sequencing and pangenomics approaches provide new opportunities to capture genome-wide variation at higher resolution and to develop practical tools for varietal discrimination, traceability, and germplasm conservation. In this study, we developed the first pangenomic framework for cultivated artichoke and evaluated pangenome-informed SNP markers for varietal fingerprinting. Whole-genome resequencing data from the Italian local ecotype Asti Sori were integrated with publicly available genomic data from representative globe artichoke and cultivated cardoon accessions to construct and annotate a pangenome. Genome-wide SNP and presence/absence variation (PAV) analyses were combined with pangenome-anchored genotyping-by-sequencing (GBS) data from 45 accessions representing the main cultivated varietal groups. The pangenome revealed a largely conserved core gene repertoire alongside a smaller accessory component, with gene accumulation curves suggesting a tendency toward saturation within the sampled cultivated germplasm. SNP- and PAV-based analyses provided complementary views of accession relationships and consistently resolved the principal cultivated groups. Across the broader germplasm panel, pangenome-anchored GBS-derived SNPs identified well-supported phylogenetic clusters corresponding to recognized varietal types. A reduced panel of 50 SNPs, selected through iterative random subsampling, retained at least 90% of the genetic diversity captured by the full dataset and reproduced its main population structure. This compact pangenome-anchored marker set provides a practical foundation for varietal fingerprinting, DUS-oriented applications, traceability, and conservation of traditional globe artichoke germplasm. Validation across independent collections will be required before routine deployment.

Plant Biology↗

bioRxiv2025

Cryptic leukemia antigens share homology with microbial epitopes and stimulate T-cell responses in healthy donors

Leukemia cells express cryptic tumor-specific antigens (TSAs) derived from aberrantly transcribed non-exomic genome sequences. These antigens are generally absent from healthy tissues yet shared across patients, making them attractive immunotherapy targets by minimizing on-target/off-tumor toxicity while offering broad applicability. However, their immunogenic potential and the nature of the T-cell repertoire they stimulate remain unknown. Cryptic antigen-specific CD8+ T cells could be expanded from healthy donor T-cell repertoires for six out of nine candidate acute leukemia cryptic TSA. T-cell receptor (TCR) and epitope sequence analysis revealed oligoclonal or near-monoclonal responses, involving shared and donor-restricted clonotypes recognizing cryptic TSAs which shared sequence homology with microbial epitopes. Orthotopic TCR replacement with cryptic TSA-specific TCR chains using a one-step CRISPR-Cas9 approach further validated the antigenic specificity and therapeutic potential of two TCRs respectively targeting cryptic TSAs from acute myeloid and lymphoid leukemia. To our knowledge, this is the first report describing functional TCRs directed against cryptic leukemia TSAs and highlights their potential as a new class of antigens for T-cell-based immunotherapies. Key pointsO_LIA high proportion of cryptic leukemia TSAs shares homology with microbial epitopes and can stimulate expansion of low-frequency T cell repertoire in healthy individuals. C_LIO_LIEx vivo expansion of cryptic TSA-specific T cells enables TCR identification that can be used to devise new T cell immunotherapies. C_LI Visual Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=122 SRC="FIGDIR/small/691479v1_ufig1.gif" ALT="Figure 1"> View larger version (30K): org.highwire.dtl.DTLVardef@1bd720dorg.highwire.dtl.DTLVardef@8ac6d6org.highwire.dtl.DTLVardef@104289aorg.highwire.dtl.DTLVardef@5a65e_HPS_FORMAT_FIGEXP M_FIG C_FIG ConclusionCryptic leukemia antigens elicit antigenic and specific T-cell responses and represents novel targets for TCR or BiTE immunotherapy.

immunology↗

bioRxiv2023

Combined inhibition of homologous PTPN1 and PTPN2 is synergistic in enhancing CD8 T cell effector functions.

Increased understanding of the modulatory pathways controlling CD8 T cell responses has led to the formulation of successful checkpoint inhibitor-based immunotherapies against cancer. However, their effectiveness is limited to a few tumor types, motivating the search for novel combinatorial strategies. PTPN1 and PTPN2 are two homologous protein tyrosine phosphatases recently proposed as potent intracellular checkpoints. Furthermore, their catalytic domain is a propitious target for small-molecule pharmacological intervention. Herein we investigated the potential effects of conditional genetic deletion of either or both phosphatases in mouse CD8 T cells, one of the main effectors in cancer immunotherapy. Our results demonstrated that hemizygous deletion of PTPN1 in a PTPN2 deficient background heightens the enhanced effector phenotype already observed in PTPN2 defective CD8 T cells. This functional gain is mediated by an autocrine IL-10 positive feedback loop. Pharmacological inhibition with a PTPN1/2 small-molecule inhibitor yielded similar results, highlighting the importance of simultaneously inhibiting both phosphatases. Our study uncovers a novel mechanism by which the downregulation of PTPN1 and PTPN2 act as a powerful tool for potentiating CD8 cytotoxic responses.

immunology↗