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Published on: April 21, 2022
Phosphoproteomic analysis of human embryonic stem cells
Laurence M Brill1, Wen Xiong, Ki-Bum Lee
1Genomics Institute of the Novartis Research Foundation, San Diego, CA 92109, USA. lbrill@burnham.org
Cell Stem Cell
|August 12, 2009
Summary
Phosphorylation is key to stem cell behavior but poorly understood. This study reveals critical receptor tyrosine kinase (RTK) signaling pathways in human embryonic stem cells (hESCs), identifying key proteins for maintaining pluripotency.
Area of Science:
- Stem cell biology
- Cellular signaling
- Proteomics
Background:
- Protein phosphorylation plays a vital role in cellular functions but remains undercharacterized in pluripotent stem cells.
- Understanding phosphorylation patterns is crucial for deciphering the mechanisms governing stem cell behavior and fate determination.
Purpose of the Study:
- To investigate and characterize protein phosphorylation in human embryonic stem cells (hESCs) and their differentiated counterparts.
- To identify key signaling pathways and proteins involved in maintaining the undifferentiated state of hESCs.
Main Methods:
- Phosphoproteomic analysis of hESCs and differentiated derivatives.
- Identification and quantification of phosphorylation sites and phosphoproteins.
- Cellular assays to validate the functional roles of identified signaling pathways.
Main Results:
- Identified 2546 phosphorylation sites on 1602 phosphoproteins.
- Found distinct phosphorylation profiles between undifferentiated hESCs and differentiated cells, with more sites on 389 proteins in hESCs and 540 in differentiated cells.
- Revealed the significant role of receptor tyrosine kinase (RTK) signaling pathways, including EGFR, VEGFR, and PDGFR, in maintaining hESC pluripotency, alongside bFGF and JNK activity.
Conclusions:
- Phosphoproteomic data provides valuable insights into protein function in hESCs.
- Specific RTK signaling pathways are critical for maintaining the undifferentiated state of hESCs.
- Integrating phosphoproteomics with transcriptomics and epigenetics enhances the understanding of hESC fate determination.
Related Concept Videos
00:58Embryonic Stem Cells
Embryonic stem (ES) cells are undifferentiated pluripotent cells, meaning they can produce any cell type in the body. This gives them tremendous potential in science and medicine since they can generate specific cell types for use in research or to replace body cells lost due to damage or disease.
00:57Embryonic Stem Cells
Embryonic stem (ES) cells were first discovered in mice in 1981 by Martin Evans. In 1998, James Thomson identified a method to isolate embryonic stem cells from humans. Human embryonic stem cells (hESCs) are obtained from 3-5 day old embryos that remain unused after an in vitro fertilization procedure.
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...
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...