We study the molecular and cellular mechanisms underlying the functional diversity of the adult reward system, cell fate choices leading to its development and how these are affected in autism spectrum disorder

For this, we use state-of-the art single cell RNA/epigenome sequencing techniques, CRISPR-mediated gene inactivation, mouse genetics, bioengineered organoids and computational tools to run multidisciplinary, collaborative projects

---

Latest news

• Leptin targets spatially diverse neuronsAugust 9, 2022

  Leptin is a hormone that is secreted by fat and signals the need to stop eating and increase energy expenditure via leptin receptors (LepR). Various hunger and reward centers in the brain contain different LepR expressing neurons. The primary leptin center is the well-studied arcuate nucleus. Other hypothalamic nuclei are less abundant in leptin receptor but also essential in encoding leptin’s actions. The composition of these LepR neurons have not been well understood.

  

  In our recently published paper in Science Reports, Nefeli Kakava of the UMC Utrecht Brain Center explore the scarce LepR population in the lateral hypothalamus. This population is known for its effects on food intake and food reward, and may be defective in eating disorders. We successfully capture the transcriptome of these neurons using TRAP-Seq. Exploration of their molecular profile confirms the expression of diverse neuropeptides and receptors. Microscopy analysis reveal their diverse spatial expression patterns. Moreover, they unravel new markers that could have significant role in energy balance. We also explore what is the transcriptional response of these neurons to energy deficit.

  

  “I am excited that we have successfully managed to capture RNA from this very rare albeit significant population of leptin responsive cells and hope our findings inspire new research”

  

  Nefeli obtained her PhD in 2020 under the supervision of Roger Adan and Onur Basak. As part of the Adan lab, she developed viral vector tools to target and manipulate the activity of brain cells involved in food reward and energy balance. In collaboration with our lab, she has profiled the hypothalamic LepR cells using TRAP-Seq and single cell genomics techniques.

• Single-cell profiling adult human neural stem cellsFebruary 25, 2022

  New paper led by Vanessa Donega of the Elly Hol lab is out in Nature communications! Single cell characterisation of the adult human subventricular zone identifies SFRP1 as a quiescence signal. Happy to have contributed as a collaborator tot his research performed at the Translational Neuroscience Department of the UMC Utrecht Brain Center

  See the original article at: https://translationalneuroscience.nl/news/donega-nscs/

  Neural stem cells (NSCs) of the subventricular zone (SVZ) remain mostly in a dormant state in the adult human brain after closure of the neurogenic period at birth. These dormant progenitors rarely proliferate or produce neurons. How an adult human NSC is maintained in this quiescent state and could be triggered to re-activate is still unclear.

  In this recent publication at Nature Communications, Vanessa Donega, Elly Hol and colleagues unravel a possible mechanism through which progenitors of the adult human SVZ are maintained in a dormant state. They used state-of-the-art single-cell RNA sequencing to profile the molecular characteristics of a major neural stem cell niche in the adult human brain. They identify the Wnt pathway antagonist SFRP1 as a possible signal that promotes neural stem cell quiescence in the aged human SVZ. Furthermore, they show that inhibition of SFRP1 stimulates neural stem cell activation both in vivo and in vitro. This work opens up future possibilities to stimulate neural stem cells of the human brain to promote repair.

  “I am very happy that this work is out, and I am excited to continue investigating the role of SFRP1 in regulating neural stem cell quiescence.” Vanessa Donega

  This work was performed primarily at our Translational Neuroscience department of the UMC Brain center. This work was supported by ZonMw, by the MAXOMOD consortium, a Ministry of Science and Technology of China grant, Theme-based Research Scheme, Health and Medical Research Fund and CUHK Direct Grant