Biology subjects

Hall, J. C.

Publications and source records attributed to Hall, J. C..

3 recordsLinked to original sources

bioRxiv2025

Patient induced pluripotent stem cells identify specificities of a reticular pseudodrusen phenotype in age-related macular degeneration

BackgroundAge-related macular degeneration (AMD) is a leading cause of vision loss. Reticular pseudodrusen (RPD), deposits on the apical side of the retinal pigment epithelium (RPE), signify a distinctive and critical AMD phenotype. Yet, their molecular basis and relationship to the conventional drusen seen in AMD remain unclear. ResultsWe generated induced pluripotent stem cell-derived RPE cells from a clinically phenotyped cohort comprising only individuals with conventional drusen (AMD/RPD-) or drusen coexisting with RPD (AMD/RPD+). From these cells, we generated single-cell transcriptomics, proteomics, and functional data to identify differences between the two cohorts. We show that AMD/RPD+ RPE cells exhibit enrichment in extracellular matrix (ECM) remodelling, cytoskeletal, and hypoxia-responsive programs, whereas AMD/RPD- RPE cells display a relatively greater representation of mitochondrial and protein homeostasis pathways. Both subtypes engaged pathways classically linked to ageing, including ECM remodelling and mitochondrial function, but differed in the direction and extent of these changes. Expression and protein quantitative trait loci (QTLs) highlight shared genetic influences on mitochondrial and iron-handling pathways, while disease-interacting eQTLs and transcriptome-wide association study identify regulatory signals that are distinctive of the RPD subtype within AMD, including through regulation of ECM. Functionally, all iPSC-derived RPE formed drusen-like deposits in vitro: AMD/RPD-lines generated more basal deposits, whereas AMD/RPD+ cells exhibited greater structural instability under bisretinoid-induced stress. ConclusionsThese findings indicate that AMD with and without RPD represent mechanistically distinct entities and provide novel insight into the molecular mechanisms underlying disease heterogeneity in AMD.

genetics↗

bioRxiv2019

Phylogeny and Multiple Independent Whole-Genome Duplication Events in the Brassicales

Whole-genome duplications (WGDs) are prevalent throughout the evolutionary history of plants. For example, dozens of WGDs have been phylogenetically localized across the order Brassicales, specifically, within the family Brassicaceae. However, while its sister family, Cleomaceae, has also been characterized by a WGD, its placement, as well as that of other WGD events in other families in the order, remains unclear. Using phylo-transcriptomics from 74 taxa and genome survey sequencing for 66 of those taxa, we infer nuclear and chloroplast phylogenies to assess relationships among the major families of the Brassicales and within the Brassicaceae. We then use multiple methods of WGD inference to assess placement of WGD events. We not only present well-supported chloroplast and nuclear phylogenies for the Brassicales, but we also putatively place Th- and provide evidence for previously unknown events, including one shared by at least two members of the Resedaceae, which we name Rs-. Given its economic importance and many genomic resources, the Brassicales are an ideal group to continue assessing WGD inference methods. We add to the current conversation on WGD inference difficulties, by demonstrating that sampling is especially important for WGD identification.

evolutionary biology↗

bioRxiv2018

How to Build a Fruit: Transcriptomics of a Novel Fruit Type in the Brassiceae

Comparative gene expression studies are invaluable for predicting how existing genetic pathways may be modified or redeployed to produce novel and variable phenotypes. Fruits are ecologically important organs because of their impact on plant fitness and seed dispersal, modifications in which results in morphological variation across species. A novel fruit type in the Brassicaceae known as heteroarthrocarpy enables distinct dispersal methods in a single fruit through segmentation via a lateral joint and variable dehiscence at maturity. Given the close relationship to Arabidopsis, species that exhibit heteroarthrocarpy are powerful models to elucidate how differences in gene expression of a fruit patterning pathway may result in novel fruit types. Transcriptomes of distal, joint, and proximal regions from Erucaria erucarioides and Cakile lanceolata were analyzed to elucidate within and between species differences in whole transcriptome, gene ontology, and fruit patterning expression profiles. Whole transcriptome expression profiles vary between fruit regions in patterns that are consistent with fruit anatomy. These transcriptomic variances do not correlate with changes in gene ontology, as they remain generally stable within and between both species. Upstream regulators in the fruit patterning pathway, FILAMENTOUS FLOWER and YABBY3, are expressed in the distal and proximal regions of E. erucarioides, but not in the joint, implicating alterations in the pathway in heteroarthrocarpic fruits. Downstream gene, INDEHISCENT, is significantly upregulated in the abscissing joint region of C. lanceolata, which suggests repurposing of valve margin genes for novel joint disarticulation in an otherwise indehiscent fruit. In summary, these data are consistent with modifications in fruit patterning genes producing heteroarthrocarpic fruits through different components of the pathway relative to other indehiscent, non-heteroarthrocarpic, species within the family. Our understanding of fruit development in Arabidopsis is now extended to atypical siliques within the Brassicaceae, facilitating future studies on seed shattering in important Brassicaceous crops and pernicious weeds.

plant biology↗