The nuclear pore Y-complex in stem cell differentiation and diseases

Le 15 avril 2026 à 12h00 Séminaire

Nuclear Pore Complexes (NPCs) are elaborate structures embedded in the nuclear envelope and composed of multiple copies of about 30 different proteins termed nucleoporins (Nups). Previous work from our team and many other labs have led to the characterization of a major structural sub-complex of NPCs, theY-complex (also named “Nup107-160 complex"), and to highlight its role in NPC assembly, its contribution to various stages of mitotic progression, and its involvement in embryonic stem cell differentiation. On the other hand, several teams have identified over the past years mutations in genes encoding Y-complex Nups in patients with an early-onset and severe kidney disease (steroid-resistant nephrotic syndrome, SRNS), and/or neuro-developmental disorders, mainly microcephaly. Although several mechanisms have been proposed, the reason why mutations in these ubiquitously expressed Nups lead to pathologies mainly affecting the kidney and/or the brain remains a mystery.

To address this question, we initially have used genome editing in pluripotent mouse embryonic stem cells (mESCs) and combined immunofluorescence analyses and gene regulation studies to characterize their implication in neuronal differentiation. To more closely mimic the “disease” condition associated with distinct nucleoporin mutations, we are currently usingpatient-derived human induced pluripotent stem cells (hiPSCs) bearing NUP mutations. Outcome of these two projects will be presented.