UC Berkeley

SIRT7 is a histone deacetylase that represses the expression of ribosomal proteins and mitochondrial ribosomal proteins to regulate the unfolded protein responses in the ER (UPRER) and the mitochondria (UPRmt). At the organismal level, SIRT7 deficiency results in the development of fatty livers and compromised maintenance of hematopoietic stem cells. Using a SIRT7 knockout mouse model, I found that SIRT7 deficiency also leads to reduced number of neural stem cells and reduced neurogenesis, suggesting that the role of SIRT7 in stem cell maintenance is conserved across tissues. I also revealed hepatic gene expression changes and metabolic characterization of SIRT7 knockout mice that are consistent with the repression of the somatotroph axis, uncovering a physiological response to loss of proteostasis.