Biology subjects

Lim, I.

Publications and source records attributed to Lim, I..

4 recordsLinked to original sources

bioRxiv2026

Haplotype-resolved genetic mapping using selfed progeny enables simultaneous genome assembly validation and trait dissection in a heterozygous plant

Genetic linkage maps are essential for genome analysis and molecular breeding, but developing suitable mapping populations remains challenging in many plant species. Approaches requiring inbred parental lines are particularly difficult to implement in plants with long generation times or severe inbreeding depression. We developed haplotype-resolved genetic mapping (HRGM) to construct linkage maps from a single heterozygous individual and its selfed progeny without requiring inbred parental lines. HRGM combines haplotype-resolved unitig assemblies from the S0 parent with genotype data from its S1 progeny, using sequence differences between the two haplotypes to define phased SNP markers. Application to Cynanchum wilfordii generated a high-density genetic map comprising 8,147 SNP markers consolidated into 464 bins across 11 linkage groups, spanning 786.4 cM. The map enabled the detection of two loci associated with root development. Recombination patterns derived from the S1 population showed strong concordance with the chromosome-scale genome assembly and exhibited recombination suppression in putative centromeric regions. HRGM integrates recombination-based genome assembly validation and trait mapping within a single framework. By using one generation of selfed progeny and obtaining linkage-phase information directly from phased assemblies, it simplifies mapping population development and extends the utility of genomic resources for genetic analysis and molecular breeding, particularly in species where selfed progeny can be obtained but conventional mapping populations are difficult to establish.

genomics↗

bioRxiv2024

The nitrite reductase activity of xanthine oxidoreductase sustains cardiovascular health

BackgroundXanthine oxidoreductase (XOR) is a multi-functional enzyme that metabolises purines generating uric acid and is a generator of reactive oxygen species. Both functions have been implicated in the pathogenesis of cardiovascular disease. More recently, a third function of XOR as a nitrite reductase has been identified and been shown to play a key role in the benefits of targeting the non-canonical pathway for nitric oxide (NO) generation in the cardiovascular disease setting. This effect has been specifically attributed to XOR dependent recovery of NO levels. However, whether XOR derived NO plays any role in maintaining cardiovascular homeostasis in health is unknown. To explore this, we used global and hepatocyte-specific Xdh-deleted mice to assess cardiovascular homeostasis. MethodsXdh+/+ and Xdh+/-, Xdhfl/fl and Xdhfl/flAlbCre+/-(HXOR KO) mice littermates, matched for sex and age, were used for in vivo cardiovascular phenotyping; blood pressure, cardiac function, endothelial reactivity, and leukocyte trafficking. Tissues from these mice were used for biochemical measurements of nitrate, nitrite, and markers of NO downstream signalling. ResultsXdh+/- and HXOR KO mice expressed significantly attenuated liver and plasma nitrite reductase activity and platelet cGMP levels versus littermate controls. These effects were associated with increased systolic blood pressure, left ventricular remodelling, and increased leukocyte activation. These effects were associated with and likely driven by endothelial dysfunction evident in both mouse models. This dysfunction was reflected by increased endothelial adhesion molecule expression (P-selectin), increased ischaemia-induced vasoconstriction, during vessel occlusion, and an impaired flow-mediated dilation response of the iliac artery in vivo. ConclusionsIn summary, XOR derived NO is critical for maintaining vascular homeostasis under physiological conditions and is key in mediating the benefits of dietary nitrate regimes in cardiovascular pathology

pharmacology and toxicology↗

bioRxiv2023

A hematopoietic stem cell subset that retains memory of prior inflammatory stress accumulates in aging and clonal hematopoiesis

Inflammation activates many blood cell types, driving aging and malignancy. Yet, hematopoietic stem cells (HSCs) survive a lifetime of infection to sustain life-long blood production. To understand HSC adaptation to inflammation, we developed xenograft inflammation-recovery models and performed single cell multiomics on isolated human HSC. Two transcriptionally and epigenetically distinct HSC subsets expressing canonical HSC programs were identified. Only one showed sustained transcriptional and epigenetic changes after recovery from inflammatory treatments. This HSC inflammatory memory (HSC-iM) program is enriched in memory T cells and HSCs from recovered COVID-19 patients. Importantly, HSC-iM accumulates with age and with clonal hematopoiesis. Overall, heritable molecular alterations in a subset of human HSCs, an adaptation to long-term inflammatory stress, may predispose to heightened age-related risk of blood cancer and infection. One-Sentence SummaryInflammation across a lifetime rewires human HSCs to produce a distinct HSC subset with both beneficial and deleterious fitness consequences.

cell biology↗

bioRxiv2021

Stress-driven tissue fluidization physically segments vertebrate somites

The precise and robust formation of embryonic structures is essential for the function of the organism. During somitogenesis, genetic traveling waves in the presomitic mesoderm orchestrate somite formation and the segmentation of the vertebrate body axis. While key molecular and genetic aspects of this process are known, the mechanical events required to robustly define sharp somite boundaries and physically segment the presomitic mesoderm remain unclear. Here we show that both mechanical noise in the tissue and somite boundary tension are optimized to define sharp somite boundaries and robustly segment the body axis. We find that a large, actomyosin-driven increase in boundary tension progressively straightens the nascent somite-somite boundary. While noise is typically believed to be detrimental to robustness, our results show how mechanical noise in the tissue, introduced by active tension fluctuations at cell contacts, is necessary to fully straighten somite boundaries and minimize variation across individuals. Chemical and optogenetic perturbations of both boundary tension and mechanical noise in the surrounding tissue show that zebrafish embryos optimally tune these quantities to the values necessary to ensure maximal somite boundary straightness. Altogether, these results reveal the physical mechanism of somite formation in zebrafish and uncover how optimal mechanical noise helps robustly shape embryonic structures.

biophysics↗