Supt16, a component of the facilitates chromatin transcription (FACT) complex, is crucial for chromatin-related processes such as transcription, replication, and repair. FACT, a heterodimer consisting of SSRP1 and SUPT16, reorganizes nucleosomes during DNA-related activities, ensuring efficient RNA Pol II elongation and nucleosome integrity [3].

Supt16 haploinsufficiency in mice (Supt16+/-) leads to abnormal cognitive and social behavior, along with a decrease in neurocytes in the cerebral cortex and hippocampus. This is due to the impairment of mouse neural stem cells (mNSCs) in the SVZ, as Supt16 haploinsufficiency affects mNSC proliferation and apoptosis. RNA-seq and chromatic immunoprecipitation sequencing assays show that it disrupts mNSC stemness by inhibiting the MAPK signal pathway [1].

In human pluripotent stem cells derived neural stem cells (hNSCs), Supt16+/- iPSCs differentiated into hNSCs exhibit impaired proliferation, cell cycle arrest, and increased apoptosis. RNA-seq analysis reveals that Supt16 haploinsufficiency inhibits the PI3K/AKT/mTOR pathway, leading to increased autophagy and dysregulated expression of proteins related to cell proliferation and apoptosis [2].

In conclusion, Supt16 is essential for the proper self-renewal of neural stem cells, with its haploinsufficiency disrupting key signaling pathways like MAPK and PI3K/AKT/mTOR. The study of Supt16 haploinsufficient mouse models has provided valuable insights into the pathogenesis of neurodevelopmental disorders, highlighting the gene's significance in neural development and disease [1,2].