Thyroid hormone influence on the brain

Work Group

Project Lead(s)

Project Status

Ongoing

Outcomes

Gene expression quantification and quality control for 16 bulk RNA-seq samples obtained from 8 mice; 2) differential expression analysis for defined contrasts; and 3) an exploration of alternative splicing for the ROBO3 gene

Collaborator Name

Bernardo Sabatini, PhD

HMS Department

Department of Neurobiology

Project Description

CCB works with the Sabatini lab on a whole-transcriptome  analysis of a mouse model to study the influence of thyroid hormone on the brain. In a differential setup between hyperthyroid mice and untreated control mice, the project investigates perturbations of thyroid-dependent transcription via a) over-expression of the wild-type thyroid receptor (WTTR), anticipated to have little to no effect, and b) expression of a dominant-negative thyroid receptor (DNTR), anticipated to disrupt thyroid-dependent transcription. To corroborate findings obtained with single-cell RNA sequencing (scRNA-seq), Dr. Sabatini and his team have obtained bulk RNA-seq data for 8 mice comprising (i) 4 biological replicates of WTTR vs. no exogenous expression in thyroid-treated mice, (ii) 2 biological replicates of DNTR vs. no exogenous expression in thyroid-treated  mice, and (iii) 2 biological replicates of WTTR vs. no exogenous expression in untreated mice. Dr. Sabatini and his team would like to analyze differential expression for the aforementioned contrasts, so CCB will help with processing, exploring, and analyzing these data. This includes RNA-seq read alignment and quantification, quality control, and differential expression analysis for comparison between sample groups. An additional question centers around alternative splicing of the thyroid-induced ROBO3 gene with two known isoforms.