Related Experiment Video
Updated: Aug 8, 2026
A Quick and Efficient Method for the Purification of Endoderm Cells Generated from Human Embryonic Stem Cells
Published on: March 3, 2016
Elimination of damaged proteins during differentiation of embryonic stem cells
Malin Hernebring1, Gabriella Brolén, Hugo Aguilaniu
1Department of Cell and Molecular Biology, Göteborg University, Box 462, 405 30 Göteborg, Sweden.
Abstract:
During mammalian aging, cellular proteins become increasingly damaged: for example, by carbonylation and formation of advanced glycation end products (AGEs). The means to ensure that offspring are born without such damage are unknown. Unexpectedly, we found that undifferentiated mouse ES cells contain high levels of both carbonyls and AGEs. The damaged proteins, identified as chaperones and proteins of the cytoskeleton, are the main targets for protein oxidation in aged tissues. However, the mouse ES cells rid themselves of such damage upon differentiation in vitro. This elimination of damaged proteins coincides with a considerably elevated activity of the 20S proteasome. Moreover, damaged proteins were primarily observed in the inner cell mass of blastocysts, whereas the cells that had embarked on differentiation into the trophectoderm displayed drastically reduced levels of protein damage. Thus, the elimination of protein damage occurs also during normal embryonic development in vivo. This clear-out of damaged proteins may be a part of a previously unknown rejuvenation process at the protein level that occurs at a distinct stage during early embryonic development.
Insights
Mammalian aging causes protein damage, but early embryonic development, particularly in mouse ES cells, eliminates this damage through differentiation. This protein clear-out may represent a novel rejuvenation process.
Area of Science:
- Cellular Biology
- Developmental Biology
- Biochemistry
Background:
- Cellular proteins accumulate damage, such as carbonylation and advanced glycation end products (AGEs), during mammalian aging.
- The mechanisms preventing damage transmission to offspring are not well understood.
- Undifferentiated mouse embryonic stem (ES) cells surprisingly harbor significant levels of damaged proteins, including chaperones and cytoskeletal proteins.
Purpose of the Study:
- To investigate the fate of damaged proteins during embryonic development.
- To determine if damaged proteins are cleared during differentiation.
- To explore the potential role of protein damage elimination in early embryonic development.
Main Methods:
- Analysis of protein damage (carbonylation and AGEs) in undifferentiated and differentiated mouse ES cells.
- Assessment of 20S proteasome activity during differentiation.
- Examination of protein damage levels in blastocysts, comparing the inner cell mass with trophectoderm cells.
Main Results:
- Undifferentiated mouse ES cells exhibit high levels of damaged proteins, primarily chaperones and cytoskeletal proteins.
- Differentiation of mouse ES cells in vitro leads to a significant reduction in damaged proteins.
- This reduction in protein damage correlates with increased 20S proteasome activity.
- In vivo, damaged proteins are concentrated in the inner cell mass of blastocysts, with lower levels in differentiating trophectoderm cells.
Conclusions:
- Embryonic development involves the elimination of damaged proteins, both in vitro and in vivo.
- This process of clearing damaged proteins may constitute a previously unrecognized protein-level rejuvenation mechanism.
- The findings suggest a critical role for protein quality control during early embryonic development.
Related Concept Videos
01:14Maintenance of the ES Cell State
00:57Embryonic Stem Cells
ES cells are grown in a culture medium where they can divide indefinitely, creating ES cell lines. Under certain conditions, ES cells can differentiate, either spontaneously into a variety of...
00:58Embryonic Stem Cells
01:22iPS Cell Differentiation
01:17Stem Cell Culture