PLX242962

GSE126358: SURF1 mutations causative of Leigh syndrome impair human neurogenesis [polyA RNA-seq]

• Organsim human
• Type RNASEQ
• Target gene
• Project ARCHS4

Mutations in the mitochondrial complex IV assembly factor SURF1 represent a major cause of Leigh syndrome (LS), a fatal neurological disorder. SURF1-deficient animals failed to recapitulate the neuronal failure of LS, which is considered an early-onset neurodegeneration. Using patient induced pluripotent stem cells (iPSCs) and genetically corrected cells, we discovered aberrant bioenergetics initiating in neural progenitor cells (NPCs) leading to impaired neuronal differentiation and maturation. iPSC-derived cerebral organoids recapitulated the neurogenesis defects and appeared smaller with reduced cortical thickness. We suggest defective neurogenesis as a central mechanism in LS pathogenesis and propose NPC function as an interventional target, which allowed us to identify SURF1 gene augmentation as a strategy for restoring neural function in this fatal disease. SOURCE: Petar Glazar (petar.glazar@mdc-berlin.de) - Rajewsky lab Max Delbrück Center for Molecular Medicine