TY  - JOUR
A1  - Resztak, Justyna A.
A1  - Wei, Julong
A1  - Zilioli, Samuele
A1  - Sendler, Edward
A1  - Alazizi, Adnan
A1  - Mair-Meijers, Henriette E.
A1  - Wu, Peijun
A1  - Wen, Xiaoquan
A1  - Slatcher, Richard B.
A1  - Zhou, Xiang
A1  - Luca, Francesca
A1  - Pique-Regi, Roger
T1  - Genetic control of the dynamic transcriptional response to immune stimuli and glucocorticoids at single-cell resolution
Y1  - 2023/06/01 
JF  - Genome Research 
JO  - Genome Research 
SP  - 839 
EP  - 856 
DO  - 10.1101/gr.276765.122 
VL  - 33 
IS  - 6 
UR  - http://genome.cshlp.org/content/33/6/839.abstract 
N2  - Synthetic glucocorticoids, such as dexamethasone, have been used as a treatment for many immune conditions, such as asthma and, more recently, severe COVID-19. Single-cell data can capture more fine-grained details on transcriptional variability and dynamics to gain a better understanding of the molecular underpinnings of inter-individual variation in drug response. Here, we used single-cell RNA-seq to study the dynamics of the transcriptional response to glucocorticoids in activated peripheral blood mononuclear cells from 96 African American children. We used novel statistical approaches to calculate a mean-independent measure of gene expression variability and a measure of transcriptional response pseudotime. Using these approaches, we showed that glucocorticoids reverse the effects of immune stimulation on both gene expression mean and variability. Our novel measure of gene expression response dynamics, based on the diagonal linear discriminant analysis, separated individual cells by response status on the basis of their transcriptional profiles and allowed us to identify different dynamic patterns of gene expression along the response pseudotime. We identified genetic variants regulating gene expression mean and variability, including treatment-specific effects, and showed widespread genetic regulation of the transcriptional dynamics of the gene expression response. 
ER  -