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Gourley, S. L.

Publications and source records attributed to Gourley, S. L..

2 recordsLinked to original sources

LRcell: detecting the source of differential expression at the sub-cell type level from bulk RNA-seq data

Given most tissues are consist of abundant and diverse sub cell-types, an important yet unaddressed problem in bulk RNA-seq analysis is to identify at which sub cell-type(s) the differential expression occur. Single-cell RNA-sequencing (scRNA-seq) technologies can answer the question, but they are often labor-intensive and cost-prohibitive. Here, we present LRcell, a computational method aiming to identify specific sub-cell type(s) that drives the changes observed in a bulk RNA-seq experiment. In addition, LRcell provides pre-embedded marker genes computed from putative single-cell RNA-seq experiments as options to execute the analyses. Using three different real datasets, we show that LRcell successfully identifies known cell types involved in psychiatric disorders and LRcell is more sensitive than even the leading deconvolution methods.

bioinformatics↗

Cell adhesion factors during adolescence support amygdalo-cortical connections and flexible action later in life

Adolescent brain development is characterized by dramatic neuronal remodeling in the prefrontal cortex. This plasticity is presumed to act in part to "set the stage" for prefrontal cortical function in adulthood, but causal relationships have largely not been verified. Integrins are cell adhesion factors that provide a link between the extracellular matrix and the intracellular actin cytoskeleton. We find that {beta}1-integrin presence in the prelimbic subregion of the prefrontal cortex (PL) during adolescence, but not adulthood, is necessary for adult mice to select actions based on reward likelihood and value. These behaviors require coordinated limbic-frontal-striatal circuits. We identified projections from the basolateral amygdala (BLA) to PL as being necessary for mice to express learned response strategies. We then visualized adolescent PL neurons receiving input from the BLA and projecting to the dorsomedial striatum (DMS), a primary striatal output by which the PL controls reward-related behavior. These projection-defined neurons had a more "adult-like" morphology relative to a general population of layer V PL neurons. {beta}1-integrin loss caused the overexpression of stubby-type dendritic spines at the expense of more mature spines, a phenotype not observed when {beta}1-integrins were silenced before or after adolescence. Together, these experiments localize {beta}1-integrin-mediated cell adhesion activity within a developing di-synaptic circuit that coordinates flexible action.

neuroscience↗