The habenula (Hb) plays a key role in processing reward information and mediating aversive responses to negative stimuli. In the recent issue of Cell Reports, Lieke van de Haar and colleagues have revealed how the cellular diversity of the mouse habenula is formed during development. In the work title “Cellular diversity of developing habenula may illuminate risk for human psychiatric disorders”, Lieke used single cell RNA sequencing, a technique that allows quantification of gene expression in thousands of cells simultaneously.
Reconstruction of lineage trajectories using computational tools revealed paths to habenula cell types. Intersectional genetics experiments by Oxana Garritsen showed that these include a physiologically distinct neuronal cell type that innervate the dorsal IPN which can be identified by Cartpt expression. Work by Lieke and Youri Adolfs using iDISCO and light sheet microscopy have shown that these cells localize to the medial habenula. The ePhys work by Danai Riga of the Meye lab found that these Cartpt+ neurons are electrophysiologically different from surrounding neurons. Finally, MAGMA analysis by Juliska Boer, who did her bachelor internship under the supervision of Lieke, revealed that developing cell populations align with human genetic risk loci of psychiatric disorders, such as the major depressive disorder.
“The habenula plays an important role in negative experiences, and is located dorsally to the thalamus and ventrally to the hippocampus…. we were interested in how the cells of the habenula are born and mature.” Lieke
Lieke performed her PhD work at the Pasterkamp lab of our Translational neuroscience department of the UMC Utrecht Brain Center. This work is a fine example of internal collaborations in the department which connect molecular, computational, genetic and electrophysiological techniques.
On Tuesday the 17th of May UMC Utrecht Brain Center and New Scientist organized ‘NewScientist Live! Hersenziekten in TivoliVredenburg. Several colleagues focused on the technologies of the future. It was an interesting evening, filled with exciting and necessary advances in brain research and patient care.
Prof. dr. Jeroen Pasterkamp and PhD student Tiziana Hey, from our own Translational Neuroscience department, starred on stage. Jeroen Pasterkamp started the evening off, highlighting important microscopic and organoid research performed in his lab. Tiziana Hey, together with 2 fellow young scientists, closed the evening, explaining research with the use of single cell sequencing techniques. Interested in reading more about this informative evening? You can find a summary of the evening on the website of New Scientist or watch the aftermovie (in Dutch).
“Brain research is like a black box: one big fascinating puzzle” T. Hey
We are very glad to disseminate the knowledge generated at the UMC Utrecth Brain Center.
Fantastic news from Elly Hol!! The Royal Netherlands Academy of Arts and Sciences (KNAW) announced that Prof. Elly Hol has been chosen as a new member. Members of the KNAW are leading scientists from all disciplines and are chosen on the basis of their scientific achievements. The KNAW has approximately 585 members. A membership is for life. In addition to Elly Hol, 21 other new members have been elected. The new members of the Academy will be installed on 12 September.
“I am very pleased with this recognition for my research on glia. I could not have done this research without the enormous efforts of all PhD students, post-docs, researchers, research analysts, and students who have worked in my group over the years in Amsterdam and Utrecht. It is also really nice to see how the group of glia researchers in the Netherlands and internationally has grown. The collaborations with (inter)national colleagues and the support of subsidy providers make it possible to discover new aspects of neuron-glia interactions in brain diseases. I am also very enthusiastic about new technologies, such as molecular single cell studies on human post-mortem brain material and functional studies in patient mini-brains, which are of great importance for my research on glia in brain diseases.”
PhD defence is a special occasion celebrating not only the graduation of a student but also the society gaining a new highly trained specialist. Last week, Andreia Duarte and Lieke van de Haar of the Pasterkamp lab have defended their PhD thesis with two in-person PhD defences at the Academiegebouw of the Utrecht University.
In her work “The Road Less Travelled: Exploring the profile and functions of non-coding RNAs in brain disease, Andreia has explored how circRNAs and tRNAs may facilitate the brain’s response in medial Temporal lobe epilepsy. She has started her new position as an R&D scientist at the VectorY.
“It was a great closure of 4.5 years of work with lots of research, learning, travelling, fun, ending in such an unforgettable day.” Andreia
Lieke built her PhD on a combination of wet lab experiments and computational tools. Her thesis titled “Isles of Molecules” defines the Habenula development at a single cell level and a new mechanism of axonal guidance. We wish her best luck in her new position as a postdoc at the Rajewsky lab at MDC, Germany.
“ It was a great day to celebrate 4,5 years of work at the University Medical Center Utrecht. I very much enjoyed the scientific discussions and having colleagues, friends and family around.” Lieke
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