Biology subjects

Solomon, C. U.

Publications and source records attributed to Solomon, C. U..

5 recordsLinked to original sources

bioRxiv2025

Dissecting the Cellular Genetics of Cardiovascular Disease Through Endothelial and Immune Compartments Profiling

BackgroundNon-communicable diseases such as coronary artery disease, atrial fibrillation, type 2 diabetes, hypertension, and others share endothelial dysfunction as one of their underlying features. The endothelium, as the interface between blood and vasculature, shapes disease onset and progression through its response to environmental cues. However, while the genetic component of these diseases has been captured by genome wide association studies (GWAS), which also highlighted a shared immune component, it remains unclear which of these disease loci exerts their effects through endothelial cells. This study identifies, and quantifies, the genetic determinants of endothelial cells molecular traits and their overlap to the common genetic variation component of these diseases. MethodsWe generated genotype, RNA-sequencing, H3K27ac ChIP-sequencing, ATAC-sequencing, and endothelial cells barrier stimuli response measurements for 100 samples of human umbilical vein endothelial cells. These were used to identify quantitative trait loci (QTL) for gene expression, transcriptional isoform usage, splice junction usage, chromatin activity and barrier response. We applied statistical colocalisation to identify the overlap between data layers, and to explain molecular QTLs contribution to GWAS disease loci. ResultsWe used molecular QTLs to identify the regulatory features of 8,214 genes, representing 36% of all expressed genes in endothelial cells. We also identified the molecular mechanisms underlying 815 loci across 16 disease GWAS. These represent between 29% and 40% of all loci for each disease, compared to the previous average of 23%. This is due to the choice of a cell type often underrepresented in tissue level data, and the inclusion of isoform, splicing and chromatin activity datasets. Furthermore, we compared the endothelial cells molecular QTLs with similar datasets in monocytes, neutrophils and CD4 T lymphocytes to shed light on the interplay between the endothelial and the immune compartments in these diseases. We identified loci acting through both the endothelial and the immune compartment, mostly with the same directionality of effect, and endothelial specific ones. ConclusionsThis work expands the knowledge of the mechanisms and genes underlying the effect of common genetic variation on non-communicable diseases having endothelial dysfunction as a shared feature. It also illustrates the interplay between endothelial cells and immune cell types in these diseases, highlighting shared and unique pathways.

genomics↗

bioRxiv2023

Identification and Characterization of novel long non-coding RNAs in vascular smooth cells

A significant portion of the RNA produced from the human genome consists of long non-coding RNAs (lncRNAs). These molecules tend to have lower levels of expression, are more specific to certain tissues, and show greater variation in expression between individuals compared to protein-coding messenger RNAs (mRNAs). LncRNAs have been linked with regulatory roles in gene expression and genome architecture. There is growing evidence that lncRNAs play important roles in many biological processes and diseases, and a number of lncRNAs have been identified as potential therapeutic targets. Here, we report the identification and characterization of the lncRNA landscape of vascular smooth muscle cells (VSMC). We used an ensemble of bioinformatics tools to identify 329 novel lncRNAs from a large VSMC RNA-Seq dataset. We found that majority of the novel lncRNAs are natural antisense transcripts of protein-coding genes. In addition, we predicted cellular localization and potential miRNAs that targets the novel lncRNAs and found that most localize in the cytoplasm and that miRNA target site ranged from 2-889 sites on each novel lncRNA. Furthermore, we identified co-expressed lncRNAs that correlate with the proliferation, migration and apoptosis of vascular smooth muscle cells. These results suggest that we have identified a diverse set of previously unknown lncRNAs that may be involved in important regulatory pathways in vascular smooth muscle cells.

bioinformatics↗

bioRxiv2019

LYS3 encodes a prolamin-box-binding transcription factor that controls embryo growth in barley and wheat

Mutations at the LYS3 locus in barley have multiple effects on grain development, including an increase in embryo size and a decrease in endosperm starch content. The gene underlying LYS3 was identified by genetic mapping and mutations in this gene were identified in all four barley lys3 alleles. LYS3 encodes a transcription factor called Prolamin Binding Factor (PBF). Its role in controlling embryo size was confirmed using wheat TILLING mutants. To understand how PBF controls embryo development, we studied its spatial and temporal patterns of expression in developing grains. The PBF gene is expressed in both the endosperm and the embryos, but the timing of expression in these organs differs. PBF expression in wild-type embryos precedes the onset of embryo enlargement in lys3 mutants, suggesting that PBF suppresses embryo growth. We predicted the down-stream target genes of PBF in wheat and found them to be involved in a wide range of biological processes, including organ development and starch metabolism. Our work suggests that PBF may influence embryo size and endosperm starch synthesis via separate gene control networks. HIGHLIGHTSO_LILYS3 encodes a transcription factor called Prolamin Binding Factor (PBF) that is expressed in grains only. C_LIO_LIWheat and barley LYS3/PBF mutants have enlarged embryos suggesting that this gene suppresses embryo growth. C_LIO_LIThe down-stream target genes of PBF in wheat are predicted to be involved in a wide range of biological processes including organ development and starch metabolism. C_LI

plant biology↗

bioRxiv2019

Programmed Cell Death in Developing Brachypodium distachyon Grain

O_LIThe normal developmental sequence in a grass grain entails the death of several maternal and filial tissues in a genetically regulated process termed programmed cell death (PCD). The progression and molecular aspects of PCD in developing grain have been reported for domesticated species like barley, rice, maize and wheat. Here, we report a detailed investigation of PCD in the developing grain of a wild model species, Brachypodium distachyon.\nC_LIO_LIWe detected PCD in developing Brachypodium grains using molecular and histological approaches. We also identified and surveyed the expression of Brachypodium orthologs of protease genes known to contribute to grain PCD.\nC_LIO_LIWe found that Brachypodium nucellus degenerates by PCD in a centrifugal pattern following anthesis, although at a slower rate compared to cultivated cereals. Mesocarp PCD was not coordinated with endosperm development. Brachypodium lacks an expansion of vacuolar processing enzymes known for their roles in nucellar PCD.\nC_LIO_LICombined with existing knowledge on grain PCD, our study suggests the importance of rapid nucellar PCD for grain size and that the pattern of mesocarp PCD affects grain shape.\nC_LI

plant biology↗

bioRxiv2019

Delineation of post-phloem assimilate transport pathway into developing caryopsis of Brachypodium distachyon

Assimilates stored in mature cereal grains are mobilized from source tissues and transported towards developing grains through the vascular bundle. Due to the lack of direct vascular connection between maternal grain vascular bundle and filial tissues, post-phloem transportation of assimilates into grain endosperm relies on transfer cells that lie between the grain vascular bundle and the endosperm. Here, we propose Caryopsis Endosperm Assimilate Acquisition Route (CEAAR) models that describes the exact path of assimilate import into caryopsis endosperms. Using fluorescent tracer dyes we also delineated the route of assimilate delivery into Brachypodium distachyon endosperm and classified it as ventral circuitous (vc-CEAAR), an assimilate import model also found in rice. Furthermore, we report a detailed anatomical study of post-phloem assimilate transport pathway in developing grains of Brachypodium distachyon. Our results highlight major anatomical similarities and differences between the grain post-phloem transfer cells of Brachypodium and those of crop species such as rice, wheat, and barley relevant to post-phloem assimilate transport.\n\nHighlightsO_LIBased on existing work, we propose Caryopsis Endosperm Assimilate Acquisition Route (CEAAR) models, that describes the exact path of assimilate import into caryopsis endosperms.\nC_LIO_LIThe structure of the post-phloem transfer cells of Brachypodium distachyon mirrors temperate and tropical cereals.\nC_LIO_LIAssimilate delivery into Brachypodium distachyon endosperm is identical to assimilate import into rice endosperm.\nC_LI

cell biology↗