Proteomics 2015, 15, 630–631
Editorial Proteomics and Developmental Biology Proteomic technologies have matured tremendously over the past decade enabling the charting of proteomes at great depth and accuracy and in a reasonably fast manner. While early proteomic applications primarily selected biological model systems that guaranteed sample supply in relatively large amounts (mainly cell lines), a more ambitious goal of the field has been to utilize proteomic technologies to gain a thorough understanding of biological processes in vivo, be it in humans or animal model systems. Indeed, developmental biology is one of the most exciting and fast-developing areas in biology inspired by the notion that many diseases are the result of derailed developmental processes. In addition, recent progress in stem cell biology has generated methodologies to study stem cells in the lab relatively easily. This has attracted the interest of scientists in technological areas, including proteomics, to embrace these methods to understand processes related to pluripotency and differentiation that are at the origin of any developing organism as well as of prominent diseases like cancer. This Focus issue collects 10 papers at the interface of proteomics and developmental biology, collectively illustrating the great diversity of proteomic workflows that are available today and the wide range of questions in developmental biology they can be applied to. Considering this from the opposite perspective, it is exactly this diversity of tools that is essential to be able to study development in all its details and in scarce biological material, including timecourse studies of protein expression, protein interactions, post-translational modifications and signaling, just to name a few. This issue starts off with a review that is right at the heart of the topic of this Focus issue: Holland and Ohlendieck describe recent achievements in sperm proteomics illustrating how a variety of proteomic techniques have been used to study gametogenesis, sperm activation and egg-sperm recognition as a fundamental theme in human developmental biology. Collectively this has led to an increased understanding of normal spermatogenesis as well as of disorders involving abnormalities in sperm cell morphology and motility that lead to male infertility. The authors also describe mouse models of spermatogenesis that should be very useful to generate biomarker candidates to improve diagnostic, prognostic and therapeutic aspects of infertility. In the second review and on a highly related topic, Fazeli and colleagues describe the role of proteomics to study early stages of human development shortly after conception. Specifically, they make a case for the need to study interactions between the embryo and its environment to capture the processes and molecules that impact on later development, possibly even in adult life. The authors describe how proteomics has contributed to understand dynamic processes in the oviduct and uterus, but also point to technical, ethical and practical limitations in studying the female reproductive tract. In the third review of this issue MeloBraga and colleagues describe how stem cells have been a rewarding model system for the development and application of a range of proteomic tools. The authors focus their review on advances in methodologies for the characterization of post-translational modifications (phosphorylation, acetylation, glycosylation) showing multiple examples how this has been used to reveal molecular pathways that are crucial in particular for neuronal differentiation. Two of the research papers in this issue aim to decipher processes during early mammalian development. Starting at the earliest developmental stage, Pfeiffer and colleagues ask the question whether proteome composition of mouse oocytes varies depending on donor strain, which could have a potential impact on ensuing developmental trajectories. Taking a SILAC LC-MSMS approach, indeed they identify several enzymes and regulatory proteins that differ in abundance between strains. Demant and colleagues have studied bovine zygotic development by performing a proteomic comparison between morulae and blastocysts that arise a few days after fertilization. By integrating two approaches combining iTRAQ labeling and LC-MSMS C 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Proteomics 2015, 15, 630–631
with saturation DIGE labeling and 2D gel electrophoresis, they identified numerous differences between the two developmental states. They identified a global surge in translational activity in blastocysts as well as altered expression of a number of specific proteins. Interestingly, the 2D-DIGE approach allowed them to identify several protein isoforms illustrating the power of this method and its complementarity to LC-based methods. Rocha et al. use mass spectrometric imaging (MSI) to study the change in lipid composition in differentiating mesenchymal stem cells to chondrocytes. This novel but quickly emerging field in mass spectrometry informs on the spatial distribution of biomolecules that is lost in ’conventional’ approaches. Indeed, MSI allowed the authors to identify phosphocholine-related ions in peripheral regions of sections at later stages of chondrogenesis. Illustrative of the diversity of approaches that are used in proteomics, Colucci-D’Amato deployed a multiplexed immuno assay based on magnetic beads. They targeted a range of cytokines in the culture media of pluripotent cells during neural differentiation. Interestingly they identified the chemokine CCL2 as a factor able to enhance neural differentiation, as the authors showed for cells lines as well as primary cells. Using Drosophila as a model system, Sap et al. investigated cellular response transduced by the developmental hormone ecdysone. From a time-course analysis, ecdysone-responsive proteins were identified in various functional categories, expanding the scope of players previously known to be involved in this pathway. Importantly, both this paper and the one by Pfeiffer et al. demonstrated that proteome differences are not always apparent at the mRNA level, emphasizing the importance of quantitative proteomics and its integration with transcriptome analysis. Nolte et al. used a pulsed SILAC approach to study fin regeneration in zebrafish. Upon fin amputation, over 5000 proteins were detected during a 3-week period, several of which were implicated in restoring fin shape. Finally, Simicevic and colleagues have established a repository of proteotypic peptides of transcription factors (TFs), allowing the design of targeted mass spectrometric detection of these biologically important yet typically low abundance proteins. Importantly, the resource is based on empirical data thereby providing evidence that indeed these peptides exist thereby increasing the likelihood that they can be observed by MRM in biological samples. I would like to thank all authors for their valuable contributions, and wish to thank the Editor-in-Chief Professor Michael Dunn and the Managing Editor Dr. Hans-Joachim Kraus for making this Focus Issue possible. I hope that this issue will be a valuable source of information demonstrating how proteomics has grown to make a great impact in the exciting field of developmental biology.
C 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim