Studying SMN Function in Post-Mitotic Cells

Our research extends to more relevant cell types for SMA, including motor neurons and muscle cells, because SMA patients often show severe motor defects and congenital heart malformations.
We are testing whether SMN is essential for nucleolar organization in these cells and whether it moves within the nucleolus after DNA damage, as observed in fibroblasts.
To do this, we created human iPSC lines with inducible SMN depletion, allowing us to reduce SMN levels at specific stages of cell differentiation. Different clones have different residual SMN amounts, mimicking mild to severe SMA patients.
These models let us study how much SMN is needed at different developmental stages for proper cell function and survival. Importantly, all clones share the same genome, so differences are solely due to SMN levels.
Together, these new cell lines will complement existing SMA iPSC models and provide a more physiologically relevant system to validate SMN’s role in nucleolar function and DNA repair.