ImageMikael Stiernstedt
Oligodendocyte lineage cells are crucial for neuronal communication and normal brain function. Impairment in these cells has been observed during aging and in various neurological disorders, yet the molecular mechanisms behind these changes remain largely unknown. Gaining insight into these processes is key for promoting healthy aging and developing effective therapies.
In the Functional Neurogenomics Lab, we tackle this important question from a novel perspective, by studying transposable elements (TEs). Despite being strong gene regulators and comprising more than half of our genome, TEs have been largely overlooked, leaving much to discover. Our previous work shows that TEs strongly influence gene expression in the human brain, often through interaction with their epigenetic repressors such as DNA methylation. This is particularly relevant because DNA methylation patterns are changing with age and disease, and play a key role in the differentiation, maturation and function of oligodendroglia linage cells. This represents our main research question: How do changes in epigenetic repression alter the impact of transposons in oligodendroglia and affect brain function?
Our research is driven by the hypothesis that alterations in DNA methylation over TEs lead to TE-derived gene expression changes and functional consequences in oligodendroglia. We aim to uncover the basic epigenetic processes that regulate TEs in this cell type and to study how age- and disease-related changes in this epigenetic repression drive TE mediated molecular and functional alterations.
Using human-derived material, including post-mortem tissue and advanced cell models, we combine cellular reprogramming with CRISPR-based gene and epigenome editing. Our multi-omics approach integrates long-read and single-cell DNA and RNA sequencing data with epigenome techniques and TE tailored bioinformatic pipelines.
Overall, our research is driven by our curiosity about gene regulation in the human brain and aims to untangle the intricate dynamics between transposable elements and their epigenetic repressors in diverse contexts. By developing TE-targeted epigenetic restoration strategies, we aim to bridge the gap between mechanistic understanding and therapeutic innovation.
Functional Neurogenomics