Stem cell proteomics is a developing field of omics that analyzes the proteomes of stem cells. The main interest of the application of proteomics on stem cells is the identification and quantification of varying proteomes that determine stem cell differentiation. The two central components to the understanding of stem cell differentiation are cell fate and cell state. Cell fate is the likelihood a cell will differentiate into a particular type of cell. Cell state is the profiling of a type of cell using a combination of unique markers that differentiate one lineage from another. Some notable markers of cell states analyzed with proteomics include surface proteins, translation rate, and post transcriptional modifications.
Stem Cells Stem cells are undifferentiated cells that are capable of self-replicating. The main types of stem cells are embryonic, adult, and induced pluripotent. Embryonic and induced pluripotent are most frequently studied using proteomics, since both types have more expansive capabilities in which it can be differentiated than adult stem cells. This is defined by the ability to create cells of all three germ layers: ectoderm, endoderm, and mesoderm. This unique undifferentiated state is also referred to as cellular plasticity as stem cells have the potential to differentiate into different types of cells. Stem cell plasticity is regulated by various factors including signaling cascades, transcription, translation, and epigenetics. These regulators can also be analyzed through proteomics to understand cell fate determination.
Techniques Mass spectrometry is the most popular technique used for analyzing stem cells. Mass spectrometry determines the mass of protein products that can then be used to infer their identity, however is not distinctive enough to be the sole marker. This led to the development of subsequent techniques based on mass spectrometry in tandem with another technique. The main techniques for identification of proteins are: Tandem mass-spectrometry (MSMS), Liquid chromatography (LC-MSMS), Shotgun proteomics, Targeted proteomics, and phospho-proteomics. The main techniques for quantification of proteins includes: Stable isotope labeling with amino acids in cell culture (SILAC), Di-methyl labeling, Isobaric tag for relative and absolute quantification (iTRAQ), Tandem mass tag (TMT), and Label-free quantification. Specific application of proteomic technology to stem cell biology include: membrane proteomics for cell surface markers, phosphoproteomics for signal transduction, shotgun proteomics for differential protein expression, interaction proteomics with protein complexes and protein-RNA interactions, protein interactions in chromatin with transcriptional regulation, and histone post transcriptional modification analysis with epigenetics. The primary study of proteomics has been in vitro as there have been continually progress within in vitro cell culture systems that mimic developmental processes that are not easily accessible in vivo.
History Marc Wilkins in 1994 was the first to describe the word "proteosome." The overall goal of stem proteomics is to determine the factors needed for cellular reprogramming by first looking at what factors determine cell-fate. The first strategy used to identify samples of cells and tissues was based on electrophoresis. Electrophoresis-based proteomics was too time consuming due to the complexity of proteins and was also limited by the number of samples to be tested at a time. These limitations were solved by advances in mass spectrometry and liquid chromatography. Mass spectrometry and Liquid chromatography are the foundational basis of the majority of techniques used for proteomics. The analysis of stem cells using proteomics started with embryonic stem cells. Current proteomic analysis of stem cells primarily focuses on induced pluripotent stem cells (iPSC). This is due to the ethical concerns regarding the use of embryonic stem cells.
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