Biology subjects

Kane, N.

Publications and source records attributed to Kane, N..

9 recordsLinked to original sources

bioRxiv2025

Platelet-Mediated Suppression of T Cell Function Drives Immune Evasion in Triple Negative Breast Cancer through the P-Selectin / PSGL-1 Pathway

Immune checkpoint inhibitors (ICIs) have demonstrated clinical promise in triple-negative breast cancer (TNBC), yet their effectiveness is often limited by acquired resistance and immune refractoriness. This underscores the urgent need to improve strategies that restore or enhance anti-tumor immunity. Platelets--long recognized for their role in hemostasis--have emerged as key immunomodulators in cancer by interacting with circulating tumor cells, shielding them from sheer stress and immune clearance while actively promoting immune evasion. Here, we uncover a previously unrecognized immunoregulatory pathway whereby platelet-derived P-selectin engages P-selectin glycoprotein ligand-1 (PSGL-1) on T cells, triggering immunosuppressive signaling and promoting T-cell exhaustion. This interaction, identified using in vitro co-culture systems and validated in in vivo mouse models of TNBC, reveals a targetable form of platelet-mediated immune suppression that contributes to ICI resistance. PSGL-1, traditionally known for mediating leukocyte trafficking, functions here as an immune checkpoint receptor, further underscoring the therapeutic relevance of this axis. Together, our findings highlight the P-selectin-PSGL-1 interaction as a novel and targetable mechanism of immune evasion and provide preclinical evidence that its disruption may enhance ICI responsiveness and improve outcomes in TNBC. Key PointsO_LITumor-associated platelets (TAPs) exhaust T-cells through P-selectin/P-selectin glycoprotein ligand-1 binding C_LIO_LIPharmaceutical blockade of P-selectin using Crizanlizumab, prevents exhaustion and allows T-cell function C_LI

cancer biology↗

bioRxiv2025

Genomic approaches to build de novo elite breeding gene pools from locally-adapted landraces

Many nascent breeding programs aim to achieve genetic gain by crossing locally elite germplasm, but a lack of systematic approaches to develop elite gene pools from locally-adapted varieties hinders their progress. Motivated by the observation of undesirable transgressive segregation in presumed elite crosses in Senegalese cereal breeding programs, we designed approaches for de novo development of elite gene pools from locally-adapted landrace-derived germplasm. We first define two types of "elite" germplasm: cis-elite, phenotypically similar and genetically homogeneous for locally-adapted traits ("acquired traits"); versus trans-elite, phenotypically similar, but genetically heterogeneous for acquired traits. Next, we defined two genomic approaches for de novo inference of elite gene pools: population-based genotypic inference (PGI) and QTL-based genotypic inference (QGI), and compared to a family-based phenotypic inference (FPI) approach. Using simulations that trace the evolution from locally-adapted landraces to elite breeding lines, we evaluate the effectiveness of these strategies in nascent forward breeding programs. QGI accurately and cost-effectively identifies both cis- and trans-elite pairs, regardless of the underlying trait architecture, while PGI is less sensitive when trait architecture is oligogenic. Over ten cycles of phenotypic recurrent selection, programs based on cis-elite crosses consistently outperformed those based on trans-elite crosses for genetic gain. The findings highlight the value of trait genetic architecture knowledge for elite gene pool development and provide a practical roadmap for elite germplasm development in modernizing breeding programs.

genetics↗

bioRxiv2025

Genetic control of the leaf ionome in pearl millet and correlation with root and agromorphological traits

Pearl millet (Pennisetum glaucum) thrives in arid and nutrient-poor environments, establishing its role as a crucial cereal crop for food security in sub-Saharan Africa. Despite its remarkable adaptability, its yields remain below genetic potential, primarily due to limited water and nutrient availability. In this study, we conducted ionomic profiling and genome-wide association studies (GWAS) in field conditions across two growing seasons to unravel the genetic basis of nutrient acquisition in pearl millet. Soil ion content analyses revealed significant differences in nutrient distribution between field sites, while certain ions, such as phosphorus (P) and zinc (Zn), consistently displayed stratified accumulation patterns across years, suggesting stable depth-dependent trends. Evaluation of a genetically diverse panel of inbred lines revealed substantial variation in leaf ion concentrations, with high heritability estimates. Correlations between leaf ion content and root anatomical or agromorphological traits highlighted the intricate interplay between genetic and environmental factors shaping leaf ion accumulation. These analyses also uncovered potential trade-offs in nutrient acquisition strategies. GWAS identified genomic regions associated with leaf ion concentrations, and the integration of genetic and gene expression data facilitated the identification of candidate genes implicated in ion transport and homeostasis. Our findings provide valuable insights into the genetic regulation of nutrient acquisition in pearl millet, offering potential targets for breeding nutrient-efficient and climate-resilient varieties. This study underscores the importance of integrating genetic, physiological, and root architectural traits to enhance agricultural productivity and sustainability in resource-constrained environments.

plant biology↗

bioRxiv2024

The evolution of heteromorphic sex chromosomes in plants

Sex chromosomes in cannabis and hop were identified a century ago because of their obvious visible differences in size (heteromorphy). However, we know little about the genes they contain that control the development of the inflorescences. Here we assembled genomes, with phased sex chromosomes, for hop and cannabis. The XY chromosomes share an origin prior to the divergence between the genera >36 MYA. Due to the inheritance patterns of the XYs, the male-specific region of the Y is highly-degenerated, with substantial gene loss, while the X shows faster rates of molecular evolution. Consistent with the theory that these species lack an active-Y system, no clear sex-determining genes reside on the Y. Instead, an X-linked homolog of aminocyclopropane-1-carboxylate synthase (ACS), that is involved in the ethylene biosynthesis pathway, determines the fate of the female inflorescence. Beyond sex determination, the sex chromosomes contribute to the sexual dimorphism in ecology and physiology and have played a role in the domestication and breeding of these species.

evolutionary biology↗

bioRxiv2023

A strongly improved assembly of the pearl millet reference genome using OxfordNanopore long reads and optical mapping

Pearl millet (Pennisetum glaucum (L.)) R. Br. syn. Cenchrus americanus (L.) Morrone) is an important crop in South Asia and sub-Saharan Africa which contributes to ensure food security. Its genome has an estimated size of 1.76 Gb and displays a high level of repetitiveness above 80%. A first assembly was previously obtained for the Tift 23D2B1-P1-P5 cultivar genotype using short-read sequencing technologies. This assembly is however incomplete and fragmented with around 200 Mb unplaced on chromosomes. We report here an improved quality assembly of the pearl millet Tift 23D2B1-P1-P5 cultivar genotype obtained with an approach combining Oxford Nanopore long reads and Bionano Genomics optical maps. This strategy allowed us to add around 200 Mb at the chromosome-level assembly. Moreover we strongly improved continuity in the order of the contigs and scaffolds wihtin the chromosomes, particularly in the centromeric regions. Notably, we added more than 100 Mb around the centromeric region on chromosome 7. This new assembly also displayed a higher gene completeness with a complete BUSO score of 98.4% using the Poales database. This more complete and higher quality assembly of the Tift 23D2B1-P1-P5 genotype now available to the community will help in the development of research on the role of structural variants, and more broadly in genomics studies and the breeding of pearl millet.

genomics↗

bioRxiv2022

Optimization of capture protocols across species targeting up to 32000 genes and their extension to pooled DNA

PremiseIn-solution based capture is becoming a method of choice for sequencing targeted sequence. Methods and resultsWe assessed and optimized a capture protocol in 20 different species from 6 different plant genus using kits from 20,000 to 200,000 baits targeting from 300 to 32,000 genes. We evaluated both the effectiveness of the capture protocol and the fold enrichment in targeted sequences. We proposed a protocol with multiplexing up to 96 samples in a single hybridization and showed it was an efficient and cost-effective strategy. We also extended the use of capture to pools of 100 samples and proved the efficiency of the method to assess allele frequency. Using a set of various organisms with different genome sizes, we demonstrated a correlation between the percentage of on-target reads vs. the relative size of the targeted sequences. ConclusionAltogether, we proposed methods, strategies, cost-efficient protocols and statistics to better evaluate and more effectively use hybridization capture.

evolutionary biology↗

bioRxiv2021

Genetic control of rhizosheath formation in pearl millet

The rhizosheath, the layer of soil that adheres strongly to roots, influences water and nutrients acquisition. Pearl millet is a cereal crop that plays a major role for food security in arid regions of sub Saharan Africa and India. We previously showed that root-adhering soil mass is a heritable trait in pearl millet and that it correlates with changes in rhizosphere microbiota structure and functions. Here, we studied the correlation between root-adhering soil mass and root hair development, root architecture, and symbiosis with arbuscular mycorrhizal fungi and we analysed the genetic control of this trait using genome wide association (GWAS) combined with bulk segregant analysis and gene expression studies. Root-adhering soil mass was weakly correlated only to root hairs traits in pearl millet. Twelve QTLs for rhizosheath formation were identified by GWAS. Bulk segregant analysis on a biparental population validated five of these QTLs. Combining genetics with a comparison of global gene expression in the root tip of contrasted inbred lines revealed candidate genes that might control rhizosheath formation in pearl millet. Our study indicates that rhizosheath formation is under complex genetic control in pearl millet and suggests that it is mainly regulated by root exudation. HighlightFormation of the rhizosheath, a layer of soil adhering to the root, is under complex genetic control in pearl millet and is mainly regulated by root exudation.

plant biology↗

bioRxiv2020

Patterns of genetic variation in a prairie wildflower, Silphium integrifolium, suggest a non-prairie origin and untapped variation available for improved breeding.

AO_SCPLOWBSTRACTC_SCPLOWO_ST_ABSPremiseC_ST_ABSUnderstanding the relationship between genetic structure and geography provides information about a species evolutionary history and can be useful to breeders interested in de novo domestication. The North American prairie is especially interesting because of its relatively recent origin and subsequent dramatic fragmentation and degradation. Silphium integrifolium is an iconic perennial American prairie wildflower targeted for domestication as an oilseed crop. Germplasm in the existing breeding program is derived from accessions collected in restricted geographic regions. We present the first application of population genetic data in this species to address the following goals (1) improve breeding programs by characterizing genetic structure and (2) identify the species geographic origin and potential targets and drivers of selection during range expansion. MethodsWe developed a reference transcriptome as a genotyping reference for samples from throughout the species range. Population genetic analyses were used to describe the distribution of genetic variation and demographic modeling was used to characterize potential processes that shaped variation. Outlier scans for selection and associations with environmental variables were used to identify loci linked to putative targets and drivers of selection. Key resultsGenetic variation partitions samples into three geographic clusters. Patterns of variation and demographic modeling suggest that the species origin is in the American southeast. Breeding program accessions are from the region with lowest observed genetic variation. ConclusionsThis iconic prairie species did not originate within the modern prairie. Breeding programs can be improved by including accessions from outside of the germplasm founding region, which has relatively little variation. The geographic structuring coupled with the identified targets and drivers of adaptation can guide collecting efforts towards populations with beneficial agronomic traits.

evolutionary biology↗

bioRxiv2018

Response to early drought stress and identification of QTLs controlling biomass production under drought in pearl millet

Pearl millet plays a major role in food security in arid and semi-arid areas of Africa and India. However, it lags behind the other cereal crops in terms of genetic improvement. The recent sequencing of its genome opens the way to the use of modern genomic tools for breeding. Our study aimed at identifying genetic components involved in early drought stress tolerance as a first step toward the development of improved pearl millet varieties or hybrids. A panel of 188 inbred lines from West Africa was phenotyped under early drought stress and well-irrigated conditions. We found a strong impact of drought stress on yield components. This impact was variable between inbred lines. We then performed an association analysis with a total of 392,493 SNPs identified using Genotyping-by-Sequencing (GBS). Correcting for genetic relatedness, genome wide association study identified QTLs for biomass production in early drought stress conditions and for stay-green trait. In particular, genes involved in the sirohaem and wax biosynthesis pathways were found to co-locate with association loci. Our results open the way to use genomic selection to breed pearl millet lines with improved yield under drought stress.

plant biology↗