Johan Jakobsson
Lead PI (Core Leadership)
Lund University
Johan Jakobsson is a Professor in the Department of Experimental Medical Sciences at Lund University, Sweden and the Director of the Lund Stem Cell Center. He studied gene therapy in the brain as a graduate student in Lund and performed his postdoctoral work with Didier Trono at EPFL focusing on transposable elements.
Recent ASAP Preprints & Published Papers
A molecular atlas of cell-type specific signatures in the parkinsonian striatum
The progressive degeneration of dopaminergic projections to the striatum is a key disease mechanism in Parkinson’s disease (PD). To define the cellular landscape in the parkinsonian striatum, we mapped the cell-type specific transcriptional landscape in early and progressive PD mouse models and in human PD stages. Our analyses revealed substantial transcriptomic changes across both neuronal and glial populations, with astrocytes and oligodendrocytes exhibiting distinct disease-associated gene expression profiles. Notably, progressive dopamine depletion uncovered differential neuronal vulnerability, identifying eccentric striatal projection neurons (SPNs) and Chst9-expressing direct-pathway SPNs as among the most resilient subtypes in both species. This cross-species resource establishes a comprehensive framework for investigating cell-state dynamics in the parkinsonian striatum and uncovers selectively vulnerable and resistant cell types that can inspire new therapeutic strategies.
Activation of transposable elements is linked to a region- and cell-type-specific interferon response in Parkinson’s disease
Parkinson’s disease (PD) is a common age-related neurodegenerative disorder involving a neuroinflammatory response, the cause of which remains unclear. Transposable elements (TE) have been linked to inflammatory states, but their potential role in PD has not been explored. Using bulk– and single nuclei RNAseq of postmortem brain tissue from four brain regions, we studied TE transcriptional activation and its correlation with neuroinflammation in PD. Over a thousand TE loci, including LINE-1s and ERVs, were highly expressed in a cell-type and region-specific manner in the human brain. Increased TE expression was found in microglia and neurons in the substantia nigra and putamen in the PD brains, but not amygdala or prefrontal cortex, compared to age-matched control tissue. This TE activation correlated with innate immune transcriptional responses, characterized by the expression of interferon-related and viral response genes, in the same brain regions. The link between an interferon response and TE activation was mechanistically confirmed using human pluripotent stem cell-derived microglia and neurons. Our findings provide a unique insight into TE transcription in the PD brain and suggests that TEs play a role in chronic neuroinflammatory processes and the progression of this neurodegenerative disorder.
