Biology subjects

Johnson, J. L.

Publications and source records attributed to Johnson, J. L..

4 recordsLinked to original sources

bioRxiv2018

Keratinocyte desmoglein 1 regulates the epidermal microenvironment and tanning response

Coordinated responses to environmental stimuli within the keratinocyte:melanocyte niche are poorly understood. Desmoglein 1 (Dsg1), a keratinocyte-specific desmosomal cell-cell adhesion protein with emerging signaling roles, is reduced by ultraviolet light radiation. Loss-of-function Dsg1 mutations elevate keratinocyte cytokines in Severe dermatitis, multiple Allergies, and Metabolic wasting (SAM) syndrome. We asked whether Dsg1 regulates keratinocyte:melanocyte paracrine communication to induce the tanning response. Dsg1-silenced keratinocytes increased Pro-opiomelanocortin mRNA and cytokine secretion. Melanocytes treated with conditioned media from Dsg1-silenced keratinocytes exhibited increased Mitf and Trp1 mRNA, melanin secretion, and dendrite length. Inhibiting the melanocyte pigment-associated melanocortin 1 receptor reduced pigment secretion in response to Dsg1-deficient conditioned media. Melanocytes incorporated into Dsg1-deficient human skin equivalents relocalized suprabasally, reminiscent of early melanoma pagetoid behavior. Dsg1 decreased in keratinocytes surrounding dysplastic nevi and early melanoma, but not benign nevi. We posit Dsg1 controls keratinocyte:melanocyte communication through paracrine signaling, which goes awry upon Dsg1 loss in melanoma development.

cell biology↗

bioRxiv2018

A cosine similarity-based method to infer variability of chromatin accessibility at the single-cell level

Cellular identity between generations of developing cells is propagated through the epigenome particularly via the accessible parts of the chromatin. It is now possible to measure chromatin accessibility at single-cell resolution using single-cell assay for transposase accessible chromatin (scATAC-seq), which can reveal the regulatory variation behind the phenotypic variation. However, single-cell chromatin accessibility data are sparse, binary, and high dimensional, leading to unique computational challenges. To overcome these difficulties, we developed PRISM a computational workflow and R package (https://github.com/stanleycai123/PRISM) that quantifies cell-to-cell chromatin accessibility variation while controlling for technical biases. Using data generated in our lab or publically available, we show that PRISM outperforms an existing algorithm, which relies on the aggregate of signal across a set of genomic regions. PRISM shows robustness to noise in low accessibility cells and reveals previously masked accessibility variation where accessible sites differ between cells but total number of accessible sites is constant. We also show that PRISM, but not an existing algorithm, finds suppressed heterogeneity of accessibility at CTCF binding sites. PRISM is a novel multidimensional scaling-based method using angular cosine distance metrics coupled with distance from the spatial centroid. PRISM takes differences in accessibility at each genomic region between single cells into account. This updated approach uncovers new biological results with profound implications on the cellular heterogeneity of chromatin architecture.

genomics↗

bioRxiv2017

Genomic responses to selection for tame/aggressive behaviors in the silver fox (Vulpes vulpes)

Animal domestications have led to a shared spectrum of striking behavioral and morphological changes. To recapitulate this process, silver foxes have been selectively bred for tame and aggressive behaviors for over 50 generations at the Institute for Cytology and Genetics in Novosibirsk, Russia. To understand the genetic basis and molecular mechanisms underlying the phenotypic changes, we profiled gene expression level and coding SNP allele frequencies in two brain tissues from 12 aggressive and 12 tame foxes. Expression analysis revealed 146 genes in prefrontal cortex and 33 genes in basal forebrain that were differentially expressed (5% FDR). These candidates include genes in key pathways known to be critical to neurological processing, including the serotonin and glutamate receptor pathways. In addition, 295 of the 31,000 exonic SNPs show significant allele frequency differences between tame and aggressive population (1% FDR), including genes with a role in neural crest cell fate determination.

evolutionary biology↗

bioRxiv2017

GAS Power Calculator: web-based power calculator for genetic association studies

MotivationStatistical power calculations are crucial in designing genetic association studies. They help guide tradeoffs between large sample sizes and detailed assessments of genotype and phenotype, help determine which studies are viable, and help interpret research findings. To facilitate widespread use of power analysis in the design and interpretation of genetic studies, it is important to enable users to calculate power and visualize the effect of different models and design choices in convenient, interactive tools that are easily accessible.\n\nResultsWe developed the Genetic Association Study (GAS) Power Calculator to provide users with a simple interface that can be compute the power of genetic association studies in a convenient browser based interface.\n\nAvailabilityThe GAS Power Calculator can be accessed from the web interface at http://csg.sph.umich.edu/abecasis/gas_power_calculator/. Source code is available at https://github.com/jenlij/GAS-power-calculator.

bioinformatics↗