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Updated: May 11, 2026
12:42
Probing for Mitochondrial Complex Activity in Human Embryonic Stem Cells
Published on: June 18, 2008
Increased proteasome activity in human embryonic stem cells is regulated by PSMD11
David Vilchez1, Leah Boyer, Ianessa Morantte
1Howard Hughes Medical Institute, Glenn Center for Aging Research, Molecular and Cell Biology Laboratory, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, California 92037, USA.
Nature
|September 14, 2012
Summary
Human embryonic stem cells (hESCs) maintain proteome stability via high proteasome activity, regulated by PSMD11 and FOXO4. This ensures stem cell identity and function.
Area of Science:
- Cell Biology
- Stem Cell Biology
- Proteostasis
Background:
- Embryonic stem cells (hESCs) are immortal in culture, requiring genome and proteome stability for identity and function.
- Asymmetric cell divisions in stem cells necessitate mechanisms to prevent the inheritance of damaged proteins.
- Understanding proteome maintenance is crucial for hESC survival and function.
Purpose of the Study:
- To investigate the mechanisms of proteome stability in human embryonic stem cells.
- To identify key proteins and pathways involved in maintaining proteostasis in hESCs.
- To explore the link between proteostasis and stem cell identity.
Main Methods:
- Analysis of proteasome activity and subunit levels in hESCs.
- Investigating the role of the 19S proteasome subunit PSMD11.
- Studying the regulation of proteasome activity by FOXO4.
- Assessing the impact of proteasome inhibition on hESC markers.
Main Results:
- hESCs exhibit high proteasome activity linked to increased PSMD11 levels and proteasome assembly.
- Ectopic PSMD11 expression enhances proteasome assembly and activity.
- FOXO4 regulates proteasome activity by modulating PSMD11 expression in hESCs.
- Proteasome inhibition in hESCs alters pluripotency and germ layer markers.
Conclusions:
- hESCs maintain proteostasis through a mechanism involving high proteasome activity, PSMD11, and FOXO4.
- This proteostasis regulation is critical for maintaining hESC identity and function.
- The findings link invertebrate longevity mechanisms to hESC biology.
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