SUPR
Ventral midbrain single cell
Dnr:

NAISS 2024/22-394

Type:

NAISS Small Compute

Principal Investigator:

Thomas Perlmann

Affiliation:

Karolinska Institutet

Start Date:

2024-04-02

End Date:

2025-05-01

Primary Classification:

30108: Cell and Molecular Biology

Allocation

Abstract

The central nervous system consists of hundreds of different nerve cell types. Understanding how this vast diversity is generated during embryonic development has remained a central scientific question in biomedical research. Midbrain dopamine (DA) neurons are critically important for motor functions, cognition and reward. The degeneration of these neurons is causing major symptoms in Parkinson's disease and DA neurotransmission is also associated with other disorders such as schizophrenia and addiction. In regenerative medicine, intense investigation is focused on generating DA neurons from stem cells for cell replacement therapy in Parkinson's disease, efforts that require knowledge about how DA neurons are normally generated. Previous studies (both our and other groups) have identified different subpopulations of dopamine lineage which are already defined at embryonic stages. The subpopulations show variable levels of vulnerability in Parkinson’s disease. The focus of this study will be the maintenance of those subpopulations in the adult stages, analysis of the axonal projections and looking for regulatory networks. For the functional analysis, several conditional knockout mouse strains will be included. We will perform RNA sequencing of isolated neurons (whole cell, nuclei) from different postnatal stages both of wild type and knockout mouse models. These large-scale data will be integrated with experimental data, which will allow us to test new hypotheses. We expect that the study will increase the understanding of the role of different dopaminergic subpopulations in PD and help generating stem cells derived dopaminergic neurons.