Stem Cells Proteomics: Prospects, Problems and Payoffs

Ralph A. Bradshaw

Mass Spectrometry Facility and Department of Pharmaceutical Chemistry
UCSF

Abstract

Human stem cells (SCs) are highly flexible with a capacity to differentiate into essentially any mature tissue or organ; as such, they hold enormous potential for the treatment of a broad spectrum of medical conditions. However, to achieve these goals, a much more detailed characterization of the functional capacities and responses of both embryonic and adult SCs to external stimuli, as well as other components of their environmental milieu, will be required to control their maintenance and differentiation both in vitro and in situ. Importantly, there is an increasing awareness that proteomics may well be able to provide important insight into these issues, thus accelerating this progress and possibly yielding new understanding of basic cellular mechanisms at the molecular level at the same time. Proteomic analyses, which generally can identify large numbers of proteins including their post-translational modifications (PTMs) in single preparations, take advantage of a variety of methods but are substantially dependent on mass spectrometry as the core technology. Such approaches have already been applied to a number of different mouse and human SC samples at different stages of response with the view of characterizing distinguishing biomarkers, such as cell surface proteins, and elucidating cellular activity, including the activation of signaling cascades and the nature of secreted proteins (secretome) during differentiation. Although these studies have collectively produced some impressive data sets, there is still a substantial lack of useful information. An overview of these initial surveys and what they have provided will be contrasted with the important goals still to be obtained.