Biology subjects

Thomas, S. M.

Publications and source records attributed to Thomas, S. M..

4 recordsLinked to original sources

bioRxiv2018

Y chromosomal noncoding RNA regulates autosomal gene expression via piRNAs in mouse testis

Majority of the genes expressed during spermatogenesis are autosomal. Mice with different deletions of Yq show sub-fertility, sterility and sperm abnormalities. The connection between Yq deletion and autosomal gene regulation is not well understood. We describe a novel mouse Yq-derived long noncoding RNA, Pirmy, which shows unprecedented number of splice variants in testis. Further, Pirmy transcript variants act as templates for several piRNAs. We identified ten differentially expressed autosome-encoded sperm proteins in mutant mice. Pirmy transcript variants have homology to 5/3UTRs of these deregulated autosomal genes. Thus, subfertility in Y-deleted mice appears to be a polygenic phenomenon that is partially regulated epistatically by the Y-chromosome. Our study provides novel insights into possible role of MSY-derived ncRNAs in male fertility and reproduction. Finally, sperm phenotypes from the Y-deleted mice seem to be similar to that reported in inter-specific male-sterile hybrids. Taken together, this study provides novel insights into possible role of Y-derived ncRNAs in male sterility and speciation.

genomics↗

bioRxiv2018

Broad-scale mercury bioaccumulation patterns in two freshwater sport fishes: testing the role of growth dilution in a warming climate

Sport fishes at the apex of aquatic food webs are indicators of mercury in the environment. However bioaccumulation of mercury in fish is a complex process that varies in space and time. Both large-scale climatic and environmental, as well as biological factors are drivers of these space-time variations. In this study, we avail a long-running monitoring program from Ontario, Canada to better understand spatiotemporal variations in fish mercury bioaccumulation. Focussing on two common large-bodied fishes (Walleye and Northern Pike), the data were first stratified by latitudinal zone (north, mid, and south) and eight temporal periods (between 1975 & 2015). A series of linear mixed-effects models (LMEMs) with latitudinal zone, time period, and their interactions as random effects were used to capture the spatial, temporal, and spatiotemporal variations in mercury bioaccumulation. The random slopes from the best-fitting LMEM were used to define bioaccumulation index and capture trends in space and time. Given the generally warming climate trend over the past 45 years, the role of growth dilution in modulating the bioaccumulation trends was also evaluated. The full model comprising of space, time and space-time interactions was the best-fit with interaction effects explaining most of the variation. Spatiotemporal trends showed overall similar patterns for both species. Growth dilution in conjunction with estimated rates of warming for different latitudinal zones failed to explain the spatiotemporal trends. Temporal trends showed contrasting bioaccumulation patterns-increasing in Northern Pike and decreasing in Walleye, suggesting temperature-driven growth dilution is more likely in latter. However, a space-for-time substitution revealed only a weak presence of growth dilution in Walleye, and it was not attributable to temperature differences. Overall, our study summarizes broad-scale variations in fish mercury and explores the role of growth dilution in shaping the observed patterns.

ecology↗

bioRxiv2017

A Comparative Study Of Endoderm Differentiation In Humans And Chimpanzees

There is substantial interest in the evolutionary forces that shaped the regulatory framework that is established in early human development. Progress in this area has been slow because it is difficult to obtain relevant biological samples. Inducible pluripotent stem cells (iPSCs) provide the ability to establish in vitro models of early human and non-human primate developmental stages. Using matched iPSC panels from humans and chimpanzees, we comparatively characterized gene regulatory changes through a four-day timecourse differentiation of iPSCs (day 0) into primary streak (day 1), endoderm progenitors (day 2), and definitive endoderm (day 3). As might be expected, we found that differentiation stage is the major driver of variation in gene expression levels, followed by species. We identified thousands of differentially expressed genes between humans and chimpanzees in each differentiation stage. Yet, when we considered gene-specific dynamic regulatory trajectories throughout the timecourse, we found that 75.. of genes, including nearly all known endoderm developmental markers, have similar trajectories in the two species. Interestingly, we observed a marked reduction of both intra-and inter-species variation in gene expression levels in primitive streak samples compared to the iPSCs, with a recovery of regulatory variation in endoderm progenitors. The reduction of variation in gene expression levels at a specific developmental stage, paired with overall high degree of conservation of temporal gene regulation, is consistent with the dynamics of developmental canalization. Overall, we conclude that endoderm development in iPSC-based models are highly conserved and canalized between humans and our closest evolutionary relative.

genomics↗

bioRxiv2016

Impact of regulatory variation across human iPSCs and differentiated cells

Induced pluripotent stem cells (iPSCs) are an essential tool for studying cellular differentiation and cell types that are otherwise difficult to access. We investigated the use of iPSCs and iPSC-derived cells to study the impact of genetic variation across different cell types and as models for studies of complex disease. We established a panel of iPSCs from 58 well-studied Yoruba lymphoblastoid cell lines (LCLs); 14 of these lines were further differentiated into cardiomyocytes. We characterized regulatory variation across individuals and cell types by measuring gene expression, chromatin accessibility and DNA methylation. Regulatory variation between individuals is lower in iPSCs than in the differentiated cell types, consistent with the intuition that developmental processes are generally canalized. While most cell type-specific regulatory quantitative trait loci (QTLs) lie in chromatin that is open only in the affected cell types, we found that 20% of cell type-specific QTLs are in shared open chromatin. Finally, we developed a deep neural network to predict open chromatin regions from DNA sequence alone and were able to use the sequences of segregating haplotypes to predict the effects of common SNPs on cell type-specific chromatin accessibility.

genomics↗