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
Novel carbon source sustains deep-sea microorganism communities
18.09.2018 | King Abdullah University of Science & Technology (KAUST)
New insights into DNA phase separation
18.09.2018 | Ulsan National Institute of Science and Technology (UNIST)
Thin-film solar cells made of crystalline silicon are inexpensive and achieve efficiencies of a good 14 percent. However, they could do even better if their shiny surfaces reflected less light. A team led by Prof. Christiane Becker from the Helmholtz-Zentrum Berlin (HZB) has now patented a sophisticated new solution to this problem.
"It is not enough simply to bring more light into the cell," says Christiane Becker. Such surface structures can even ultimately reduce the efficiency by...
A study in the journal Bulletin of Marine Science describes a new, blood-red species of octocoral found in Panama. The species in the genus Thesea was discovered in the threatened low-light reef environment on Hannibal Bank, 60 kilometers off mainland Pacific Panama, by researchers at the Smithsonian Tropical Research Institute in Panama (STRI) and the Centro de Investigación en Ciencias del Mar y Limnología (CIMAR) at the University of Costa Rica.
Scientists established the new species, Thesea dalioi, by comparing its physical traits, such as branch thickness and the bright red colony color, with the...
Scientists have succeeded in observing the first long-distance transfer of information in a magnetic group of materials known as antiferromagnets.
An international team of researchers has mapped Nemo's genome, providing the research community with an invaluable resource to decode the response of fish to...
Graphene is considered a promising candidate for the nanoelectronics of the future. In theory, it should allow clock rates up to a thousand times faster than today’s silicon-based electronics. Scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) and the University of Duisburg-Essen (UDE), in cooperation with the Max Planck Institute for Polymer Research (MPI-P), have now shown for the first time that graphene can actually convert electronic signals with frequencies in the gigahertz range – which correspond to today’s clock rates – extremely efficiently into signals with several times higher frequency. The researchers present their results in the scientific journal “Nature”.
Graphene – an ultrathin material consisting of a single layer of interlinked carbon atoms – is considered a promising candidate for the nanoelectronics of the...
03.09.2018 | Event News
27.08.2018 | Event News
17.08.2018 | Event News
18.09.2018 | Materials Sciences
18.09.2018 | Materials Sciences
18.09.2018 | Information Technology