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Updated: Jun 21, 2026

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Light-mediated Reversible Modulation of the Mitogen-activated Protein Kinase Pathway during Cell Differentiation and Xenopus Embryonic Development
Published on: June 15, 2017
Phosphorylation dynamics during early differentiation of human embryonic stem cells
Dennis Van Hoof1, Javier Muñoz, Stefan R Braam
1Developmental Biology and Stem Cell Research, Hubrecht Institute, Utrecht, The Netherlands.
Cell Stem Cell
|August 12, 2009
Summary
Human embryonic stem cells (hESCs) undergo rapid proteome remodeling during differentiation. Key phosphorylation events and kinase activities, including CDK1/2, regulate self-renewal and lineage specification.
Area of Science:
- Stem cell biology
- Proteomics
- Cell signaling
Background:
- Pluripotent stem cells possess unique protein networks that change during differentiation.
- The mechanisms governing these proteomic changes are not fully understood.
Purpose of the Study:
- To analyze the proteome and phosphoproteome of human embryonic stem cells (hESCs) during differentiation.
- To identify key signaling pathways and kinases involved in hESC self-renewal and differentiation.
Main Methods:
- Quantitative mass spectrometry was used to analyze the (phospho)proteome of hESCs during BMP-induced differentiation.
- Kinase-substrate relationships were predicted using the proteomic data.
Main Results:
- Over 5000 proteins and 3000 phosphorylation sites were identified in hESCs.
- Approximately 50% of phosphosites were regulated within 1 hour of differentiation induction.
- CDK1/2 kinases were identified as central regulators of hESC self-renewal and lineage specification.
Conclusions:
- Differentiation involves rapid and complex remodeling of phosphorylation networks in hESCs.
- The study provides a valuable resource of the hESC (phospho)proteome for future research.
- CDK1/2 plays a critical role in controlling hESC fate decisions.
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Phosphorylation
The addition or removal of phosphate groups from proteins is the most common chemical modification that regulates cellular processes. These modifications can affect the structure, activity, stability, and localization of proteins within cells as well as their interactions with other proteins.
During phosphorylation, protein kinases transfer the terminal phosphate group of ATP to specific amino acid side chains of substrate proteins. Serine, threonine, and tyrosine are the most commonly...
During phosphorylation, protein kinases transfer the terminal phosphate group of ATP to specific amino acid side chains of substrate proteins. Serine, threonine, and tyrosine are the most commonly...
Maintenance of the ES Cell State
The cells of the blastocyst inner cell mass only remain pluripotent for a short time. This state of pluripotency and self-renewal can be maintained in embryonic stem (ES) cell culture by adding specific chemicals or growth factors to ensure the cells can continue dividing and later differentiate into different cell types. In some cases, the cells are grown on a feeder layer of differentiated cells, which provides the growth factors and extracellular matrix components necessary for stem cell...

