The data may help stem cell researchers understand the mechanisms that determine whether stem cells divide or differentiate, what types of cells they become and how to control those complex mechanisms to facilitate development of new therapies. The study was published in the August 6 issue of the journal Cell Stem Cell.
Protein phosphorylation, the biochemical process that modifies protein activities by adding a phosphate molecule, is central to cell signaling. Using sophisticated phosphoproteomic analyses, the team of Sheng Ding, Ph.D., associate professor at TSRI, Evan Y. Snyder, M.D., Ph.D., professor and director of Burnham’s Stem Cell and Regenerative Biology program, and Laurence M. Brill, Ph.D., senior scientist at Burnham’s Proteomics Facility, catalogued 2,546 phosphorylation sites on 1,602 phosphoproteins. Prior to this research, protein phosphorylation in hESCs was poorly understood. Identification of these phosphorylation sites provides insights into known and novel hESC signaling pathways and highlights signaling mechanisms that influence self-renewal and differentiation.
“This research will be a big boost for stem cell scientists,” said Dr. Brill. “The protein phosphorylation sites identified in this study are freely available to the broader research community, and researchers can use these data to study the cells in greater depth and determine how phosphorylation events determine a cell’s fate.”
The team performed large-scale, phosphoproteomic analyses of hESCs and their differentiated derivatives using multi-dimensional liquid chromatography and tandem mass spectrometry. The researchers then used the phosphoproteomic data as a predictive tool to target a sample of the signaling pathways that were revealed by the phosphorylated proteins in hESCs, with follow-up experiments to confirm the relevance of these phosphoproteins and pathways to the cells. The study showed that many transcription regulators such as epigenetic and transcription factors, as well as a large number of kinases are phosphorylated in hESCs, suggesting that these proteins may play a key role in determining stem cell fate. Proteins in the JNK signaling pathway were also found to be phosphorylated in undifferentiated hESCs, which suggested that inhibition of JNK signaling may lead to differentiation, a result that was confirmed in hESC cultures.
These methods were extremely useful to discover novel proteins relevant to the human embryonic stem cells. For example, the team found that phosphoproteins in receptor tyrosine kinase (RTK) signaling pathways were numerous in undifferentiated hESCs. Follow-up studies used this unexpected finding to show that multiple RTKs can support hESCs in their undifferentiated state.
This research shows that phosphoproteomic data can be a powerful tool to broaden understanding of hESCs and how their ultimate fate is determined. With this knowledge, stem cell researchers may be able to develop more focused methods to control hESC differentiation and move closer to clinical therapies.
The protein phosphorylation data is available on the Cell Stem Cell website, as well as on the PRIDE website, www.ebi.ac.uk/pride.About Burnham Institute for Medical Research
Josh Baxt | Newswise Science News
Further reports about: > Medical Wellness > RTK > Stem cell innovation > TSRI > Tick Size > cell death > drug discovery > embryonic stem cell > medical research > methanol fuel cells > phosphoproteomic data > signaling pathway > stem cell research > stem cells > transcription factor > transcription regulators
Symbiotic bacteria: from hitchhiker to beetle bodyguard
28.04.2017 | Johannes Gutenberg-Universität Mainz
Nose2Brain – Better Therapy for Multiple Sclerosis
28.04.2017 | Fraunhofer-Institut für Grenzflächen- und Bioverfahrenstechnik IGB
More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.
Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...
Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.
"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...
The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.
Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...
The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...
Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.
Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...
28.04.2017 | Event News
20.04.2017 | Event News
18.04.2017 | Event News
28.04.2017 | Medical Engineering
28.04.2017 | Earth Sciences
28.04.2017 | Life Sciences