Single-cell RNA-sequencing is increasingly used to map the cellular heterogeneity of complex tissues. For example, more than 300 studies profiled a total of over 44 million cells across different brain regions, ages, and species. Since different research groups usually specialize in different cell-type compartments, these datasets usually differ in terminology and annotation depth. Our understanding of cellular diversity can be greatly enhanced by integrating these datasets to obtain a comprehensive atlas. In a recent publication, Lieke Michielsen, Marcel Reinders and Ahmed Mahfouz, in collaboration with the group of Fabian Theis (Helmholtz Centrum München), present ‘treeArches’, a framework to automatically build and update such reference atlases with a corresponding cell-type hierarchy. The atlas can be used to transfer cell annotations to new unlabeled datasets, facilitating reproducible analysis.

Recently, BRAINSCAPES PI Dr. Ingo Willuhn and his team were awarded an NWO VICI grant for their research into the function of serotonin and dopamine across brain regions. While there are already quite extensive insights into the individual action of these two neuromodulators, there is little understanding of the combined effects of these two systems on the brain. The VICI grant will allow Dr. Willuhn and his team to study interactive dopamine and serotonin signals in multiple brain regions. With this they aim to improve knowledge on the neurobiology of dysregulated behaviors, such as impulsivity which is a core symptom of several psychiatric disorders. Thus, ultimately, the findings may lead to the improved treatment of psychiatric disorders. Now that the good news has been received, Dr. Willuhn is organizing things to get started on the research. We have asked him a few questions on how things are going.

In their review recently published in Nature Reviews Neuroscience, Oxana Garritsen, Eljo van Battum, Laurens Grossouw and Jeroen Pasterkamp provide a comprehensive overview of the different molecular subsets and heterogeneity of dopaminergic neurons in the ventral midbrain of mice and humans. The authors first compare the currently defined subsets and then address molecular mechanisms that generate this diversity and that regulate subset positioning and target innervation in embryonic and early postnatal development. In addition, axonal wiring mechanisms and biological functions of dopaminergic neuron subtypes are extensively discussed. To further understand and treat diseases related to dopaminergic neurons, such as Parkinson disease, this review highlights the necessity of obtaining more extensive knowledge on midbrain dopamine neuron heterogeneity.

On February 22nd a BRAINSCAPES Career afternoon was organized by our Career and Training Committee. The aim of the event was to offer our PhD students and post-doctoral researchers the opportunity to gain practical insights into different career paths after completing a PhD or post-doctoral research period. As such we invited two consortium members and two external speakers to tell their career story. The interactive setup and lively discussions gave interesting insights which are hopefully of value for our new talents in shaping their own future career path.

In a study published in Nature Genetics, Cato Romero, Mats Nagel, and Sophie van der Sluis teamed up with colleagues from the Complex Trait Genetics department and the Million Veteran Program to scrutinize the genetic similarity of twelve psychiatric disorders. Besides identifying shared genes and biological substrates between pairs of disorders, they also elucidated the challenges jeopardizing the future success of cross-trait genetic research. 

In a study published in Molecular Psychiatry on Nov 24th, three Brainscapes teams across two work packages worked together to optimize statistical power for iPSC-based study designs. Their analyses demonstrate that published case-control iPSC studies are generally underpowered. 

On Friday, September 30, the BRAINSCAPES annual meeting was held in Leiden at the CORPUS congress center. Over 50 members participated in the event and well represented the 7 institutes that are involved in the project.

Researchers from UMC Utrecht characterized neurons in the ventral tegmental area that respond to stress, paving the way for future research into the functional contribution of this population to stress-driven changes in reward processing.