Supt16, a component of the facilitates chromatin transcription (FACT) complex, is crucial for chromatin-related processes. FACT is involved in DNA transcription, replication, and repair, ensuring efficient RNA Pol II elongation and nucleosome integrity. Supt16 is associated with pathways like MAPK, PI3K/AKT/mTOR, and is important in maintaining the stemness of neural stem cells, thus having overall significance in neurodevelopment [1,2,3].

In Supt16+/- mouse models, abnormal cognitive and social behavior was observed. The number of neurocytes in the cerebral cortex and hippocampus decreased due to impaired mouse neural stem cells (mNSCs) in the SVZ. Supt16 haploinsufficiency affected mNSC proliferation and apoptosis by disrupting the MAPK signal pathway [1]. In human-derived neural stem cells (hNSCs) from Supt16+/- induced pluripotent stem cells, there was impaired proliferation, cell cycle arrest, and increased apoptosis. RNA-seq analysis showed that Supt16 haploinsufficiency inhibited 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 proliferation and apoptosis regulation of neural stem cells. The study of Supt16-deficient mouse models has provided insights into the pathogenesis of neurodevelopmental disorders, highlighting its significance in understanding the role of chromatin regulators in neural development and associated diseases [1,2].

References:

1. Wang, Junwen, Zhu, Xintong, Dai, Limeng, Bai, Yun, Guo, Hong. . Supt16 haploinsufficiency causes neurodevelopment disorder by disrupting MAPK pathway in neural stem cells. In Human molecular genetics, 32, 860-872. doi:10.1093/hmg/ddac240. https://pubmed.ncbi.nlm.nih.gov/36226587/

2. Wang, Junwen, Wang, Ziyi, Dai, Limeng, Bai, Yun, Guo, Hong. 2023. Supt16 Haploinsufficiency Impairs PI3K/AKT/mTOR/Autophagy Pathway in Human Pluripotent Stem Cells Derived Neural Stem Cells. In International journal of molecular sciences, 24, . doi:10.3390/ijms24033035. https://pubmed.ncbi.nlm.nih.gov/36769360/

3. Mylonas, Constantine, Tessarz, Peter. 2018. Transcriptional repression by FACT is linked to regulation of chromatin accessibility at the promoter of ES cells. In Life science alliance, 1, e201800085. doi:10.26508/lsa.201800085. https://pubmed.ncbi.nlm.nih.gov/30456357/