Archives: Onur Basak

Basak lab

Single cell biology of neural cell identity

The cellular diversity of the human brain is immense, which is generated through evolutionarily conserved developmental mechanisms that are well-timed. The system is robust enough to create functional masterpiece; yet is susceptible to failure that may lead to cognitive dysfunction or malignant growth.

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 linked to the progression of time. 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

1. What are the molecular/epigenetic mechanisms underlying the functional diversity in the adult reward system?

The ventral tegmental area (VTA) is part of the reward system and is characterised as having a heterogeneous cell population that are organized in neural populations that exhibit a more gradual transition, making it difficult to define VTA borders. Extensive research has been done on the VTA, however not on a single cell level. As part of the BRAINSCAPES consortium, we are using single cell RNA-sequencing/ChIC-sequencing to generate reference atlases of the diverse cell populations within the VTA.

Our project will provide a new resource whose quality, precision and depth exceeds current literature. This data can be reused by researchers analysing traits linked to different mental disorders, such as depression, as well as those working on neurodegenerative disorders that affect the dopaminergic system, such as Parkinson’s Disease.

We also aim to determine how histone methylation contributes to the cellular heterogeneity in the adult brain and determine if long term histone modifications play a role in eating and stress disorders.

Single molecule FISH analysis of the dopaminergic system.

2. What are the developmental mechanisms leading to this cellular diversity?

The cellular diversity of the reward system is just being discovered. Its developmental origins is yet to be fully understood. Determining the origins of this diversity may help us better understand how our brain is build, as well as whether the underlying molecular program is affected in neurodevelopmental disorders.

We aim to delineate the molecular and cellular mechanisms behind epigenetic regulation of cell fate decisions of neural stem cells (NSCs) during the development of the reward system. For this, we use mouse genetics, bioengineered and pattern organoids, CRISPR-mediate gene ablation and computational tools.

Our group is part of the Utrecht Bioinformatics Center that performs Life Science research using big data analysis on DNA, genes, proteins and cells.. For more information please visit https://ubc.uu.nl/user/obasak/

You can access our lab webpage through here

Basak lab

Group members

Dr. Onur Basak

How does the diversity of the brain emerge? Can we define molecular basis for the functional diversity of our brain? Is there a molecular signature of time? These curiosity-driven questions have led my path, which started as a molecular biologist and to the fields of developmental neuroscience and adult somatic stem cells. I was fascinated by the world of single cell genomics, which my group employs to study the development and diversity of Brain's reward system.

mouse genetics, organoids, single cell genomics, neural stem cells

Tiziana Hey, MSc

PhD student

Generating a single cell RNAseq/ChIC-seq reference atlas of the adult mouse VTA as part of the BRAINSCAPES consortium and determining how histone methylation contributes to the cellular heterogeneity and long term differences in perturbation within the reward system.

Single-cell omics, immunohistochemistry, Ventral Tegmental Area (VTA), cell/nuclei isolation from mouse brain.

Keith Garner

Senior Research Technician

Assisting the group primarily with cell culture, molecular biology and genotyping. Master of modified lenti- and AAV viruses. His new hobby is the cell/nuclei sorting.

Basak lab

Saglam-Metiner P, Yildirim E, Dincer C, Basak O, Yesil-Celiktas O. Humanized brain organoids-on-chip integrated with sensors for screening neuronal activity and neurotoxicity. Mikrochim Acta. 2024 Jan 3;191(1):71. doi: 10.1007/s00604-023-06165-4. PMID: 38168828
Kakava-Georgiadou N, Drkelic V, Garner KM, Luijendijk MCM, Basak O, Adan RAH. Molecular profile and response to energy deficit of leptin-receptor neurons in the lateral hypothalamus. Sci Rep. 2022 Aug 4;12(1):13374. doi: 10.1038/s41598-022-16492-w. PMID: 35927440; PMCID: PMC9352899
van de Haar LL, Riga D, Boer JE, Garritsen O, Adolfs Y, Sieburgh TE, van Dijk RE, Watanabe K, van Kronenburg NCH, Broekhoven MH, Posthuma D, Meye FJ, Basak O, Pasterkamp RJ. Molecular signatures and cellular diversity during mouse habenula development. Cell Rep. 2022 Jul 5;40(1):111029. doi: 10.1016/j.celrep.2022.111029. Epub 2016 Dec 8. PMID: 35793630
Schneider J, Weigel J, Wittmann MT, Svehla P, Ehrt S, Zheng F, Elmzzahi T, Karpf J, Paniagua-Herranz L, Basak O, Ekici A, Reis A, Alzheimer C, Ortega de la O F, Liebscher S, Beckervordersandforth R. Astrogenesis in the murine dentate gyrus is a life-long and dynamic process. EMBO J. 2022 Jun 1;41(11):e110409. doi: 10.15252/embj.2021110409. Epub 2022 Apr 22. PMID: 35451150
Stenudd M, Sabelström H, Llorens-Bobadilla E, Zamboni M, Blom H, Brismar H, Zhang S, Basak O, Clevers H, Göritz C, Barnabé-Heider F, Frisén J. Identification of a discrete subpopulation of spinal cord ependymal cells with neural stem cell properties. Cell Rep. 2022 Mar 1;38(9):110440. doi: 10.1016/j.celrep.2022.110440. PMID: 35235796
Donega V, van der Geest AT, Sluijs JA, van Dijk RE, Wang CC, Basak O, Pasterkamp RJ, Hol EM. Single-cell profiling of human subventricular zone progenitors identifies SFRP1 as a target to re-activate progenitors. Nat Commun. 2022 Feb 24;13(1):1036. doi: 10.1038/s41467-022-28626-9. PMID: 35210419; PMCID: PMC8873234

Recent papers

Basak lab