STAMBP is required for long-term maintenance of neural progenitor cells derived from hESCs

Mutations in STAMBP have been well-established to cause congenital human microcephaly-capillary malformation (MIC-CAP) syndrome, a rare genetic disorder characterized by global developmental delay, severe microcephaly, capillary malformations, etc.We report here that STAMBP is dispensable for the pluripotency maintenance or neural differentiation of hESCs. However, neural progenitor cells (NPCs) derived from STAMBP-deficient hESCs fail to be long-term maintained/expanded in vitro. We identified the anti-apoptotic protein CFLAR is down-regulated in those affected NPCs and ectopic expression of CFLAR rescues NPC defects induced by STMABP-deficiency. Overall design: RNA-seq analysis revealed that apoptosis related genes are enriched in up-regulated genes in mutants neural progenitor cells when comparing with WT nerual progenitor cells and both up-regulated and down-regulated genes in KO NPCs are partially restored in KO+CFLAR NPC.