PomboLab

Rbfox1 and many other genes with changes in 3D genome structure are most highly expressed in a DN sub-type of the medial VTA, known to project to secondary addiction regions. Our work suggests that these cells may be especially sensitive to the first cocaine exposure. 6/6

Chromatin decondensation occurs at many addiction genes, but the splicing factor gene Rbfox1 becomes most extensively unfolded only after 14 days! This progressive and long-lasting cascade of disruption could provide new insights into addiction inception and relapse. 5/6

We find that the cocaine-induced rewiring of 3D genome structure occurs at all scales of genome topology (TADs, loops, compartments, chromatin (de)condensation) consistently affecting cocaine-, addiction- and synaptic plasticity associated genes. 4/6

After a single cocaine exposure, we uncover massive reorganization of 3D genome structure in mouse midbrain dopaminergic neurons (DNs) which remarkably last or become worse after 2 weeks of abstinence, well beyond previously described transcriptional and synaptic effects. 3/6

Given the post-pandemic surge in global cocaine and poly-drug use, as well as the ongoing opioid crisis in North America, there is an urgent need to understand the effects of initial exposures to drugs of abuse and the inception of addiction. 2/6

What are the molecular effects of a single drug exposure 💉 on reward system #dopamine neurons 🧠? We found an unexpected role of 3D genome 🧬 structure in long-term cellular memory of a single #cocaine exposure. @domSzabo @vedranfranke @WarrenWinick @apombo1 @BIMSB_MDC 1/6

🌱A huge thanks to the @Co_Biologists and to all the reviewers involved on planting our paper as a cherry blossom tree @For_Biologists 🌸 5/5

Splicing alterations precede gene expression events and morphological changes 4/5

Single-cell RNA-seq reveals heterogeneity of pluripotent states in Srm2 knockout stem cells 3/5

Srrm2-related gene expression changes are associated with embryo development processes and enriched in SRF targets 2/5

We show Srrm2 heterozygosity leads to loss of stemness and extensive gene expression changes 1/5

A big thank you to the fantastic reviewers and editor who highly encouraged us to push concepts to the next level. As a bonus, below is our covert art submission inspired from Dali’s Persistence of Memory, illustrated by lead author @WarrenWinick #SciArt 7/7

Lastly, we demonstrate that sensory receptor genes form strong clusters of contacts in brain cells. These gene clusters are more strictly found within repressive B compartment regions in brain cells, despite having almost no expression in brain cells or in stem cells. 6/7

Together with @LonnieRWelch and fantastic PhD student Yingnan Zhang, we show that the most differential contacts between neuronal subtypes often contain differentially expressed genes, and are rich with networks of accessible and highly expressed transcription factor motifs. 5/7

One of the most striking findings was the massive decondensation, or ‘melting’, of long genes when highly expressed or with accessible chromatin. Melting was often accompanied by localization changes, typically towards the interior of the chromosome. 4/7

We uncover that specialized brain cells contain highly specific 3D genome structures at multiple genomic scales. For example, only 14% of large-scale TAD borders are common to all cell-types, while cell-type unique borders contain genes relevant for specialized functions. 3/7

Anita @anamifernandes is officially a Doctor! Congratulations! Congratulations too to her supervisors @apombo1 and @EstebanMazzoni. Anita's research was focused on deciphering the role of RNAPolII in circRNA formation. #phdlife #WomenInSTEM #RNAPolII #circRNA