HSP60 is required for stemness and proper differentiation of mouse embryonic stem cells

Embryonic stem cells (ESCs) are metabolically distinct from their differentiated counterparts. ESC mitochondria are less complex and fewer in number than their differentiated progeny. However, few studies have examined the proteins responsible for differences in mitochondrial structure and function between ESCs and somatic cells. Therefore, in this study, we aimed to investigate the differences between mitochondrial proteins in these two cell types. We demonstrate that HSP60 is more abundant in mouse ESC mitochondria than in mouse embryonic fibroblasts. Depletion of HSP60 inhibited mouse ESC proliferation and self-renewal, characterized by decreased OCT4 expression. HSP60 depletion also enhanced apoptosis during mouse ESC differentiation into embryoid bodies. Our results suggest that HSP60 expression has an essential role in ESC self-renewal and survival of differentiated cells from ESCs. Stem cells: Mitochondrial protein regulates self-renewal High levels of Heat Shock Protein 60 (HSP60) in mitochondria are required for self-renewal of mouse embryonic stem cells (mESCs). Myung-Kwan Han and colleagues at the National University Medical School in Jeonju, Korea, carried out a detailed comparison of these energy-producing organelles in mESCs and in a specialized, differentiated cell type: mouse embryonic fibroblasts (MEFs). Both the function and weight of mitochondria in mESCs were reduced compared to MEFs. Analyses of the mitochondrial protein composition in both cell types revealed significantly higher levels of HSP60 in mESCs. Depletion of HSP60 in mESCs not only prevented proliferation and self-renewal, but also led to cell death during differentiation. These findings highlight an important role for mitochondrial HSP60 in maintaining the ability of stem cells to self-renew and survive the differentiation process.