@article {501,
	title = {A quantitative metabolomics peek into planarian regeneration. [Mass spectrometry - Metabolomics]},
	journal = {Analyst},
	volume = {140},
	year = {2015},
	month = {2015 May 21},
	pages = {3445-64},
	abstract = {<p class="rtejustify">The fresh water planarian species Schmidtea mediterranea is an emerging stem cell model because of its capability to regenerate a whole animal from a small piece of tissue. It is one of the best model systems to address the basic mechanisms essential for regeneration. Here, we are interested in studying the roles of various amines, thiols and nucleotides in planarian regeneration, stem cell function and growth. We developed mass spectrometry based quantitative methods and validated the differential enrichment of 35 amines, 7 thiol metabolites and 4 nucleotides from both intact and regenerating planarians. Among the amines, alanine in sexual and asparagine in asexual are the highest (\&gt;1000 ng/mg) in the intact planarians. The levels of thiols such as cysteine and GSH are 651 and 1107 ng mg(-1) in planarians. Among the nucleotides, the level of cGMP is the lowest (0.03 ng mg(-1)) and the level of AMP is the highest (187 ng mg(-1)) in both of the planarian strains. We also noticed increasing levels of amines in both anterior and posterior regenerating planarians. The blastema from day 3 regenerating planarians also showed higher amounts of many amines. Interestingly, the thiol (cysteine and GSH) levels are well maintained during planarian regeneration. This suggests an inherent and effective mechanism to control induced oxidative stress because of the robust regeneration and stem cell proliferation. Like in intact planarians, the level of cGMP is also very low in regenerating planarians. Surprisingly, the levels of amines and thiols in head regenerating blastemas are \~{}3 times higher compared to those for tail regenerating blastemas. Thus our results strongly indicate the potential roles of amines, thiols and nucleotides in planarian regeneration.</p>
},
	keywords = {Animals, Calibration, Chromatography, High Pressure Liquid, Limit of Detection, Metabolomics, Planarians, Reference Standards, Regeneration, Reproduction, Asexual, Species Specificity, Tandem Mass Spectrometry},
	issn = {1364-5528},
	doi = {10.1039/c4an02037e},
	author = {Natarajan, Nivedita and Ramakrishnan, Padma and Lakshmanan, Vairavan and Palakodeti, Dasaradhi and Rangiah, Kannan}
}
@article {518,
	title = {Vertebrate Hedgehog is secreted on two types of extracellular vesicles with different signaling properties. (Mass spectrometry - Proteomics)},
	journal = {Sci Rep},
	volume = {4},
	year = {2014},
	month = {2014 Dec 08},
	pages = {7357},
	abstract = {<p>Hedgehog (Hh) is a secreted morphogen that elicits differentiation and patterning in developing tissues. Multiple proposed mechanisms to regulate Hh dispersion includes lipoprotein particles and exosomes. Here we report that vertebrate Sonic Hedgehog (Shh) is secreted on two types of extracellular-vesicles/exosomes, from human cell lines and primary chick notochord cells. Although largely overlapping in size as estimated from electron micrographs, the two exosomal fractions exhibited distinct protein and RNA composition. We have probed the functional properties of these vesicles using cell-based assays of Hh-elicited gene expression. Our results suggest that while both Shh-containing exo-vesicular fractions can activate an ectopic Gli-luciferase construct, only exosomes co-expressing Integrins can activate endogenous Shh target genes HNF3β and Olig2 during the differentiation of mouse ES cells to ventral neuronal progenitors. Taken together, our results demonstrate that primary vertebrate cells secrete Shh in distinct vesicular forms, and support a model where packaging of Shh along with other signaling proteins such as Integrins on exosomes modulates target gene activation. The existence of distinct classes of Shh-containing exosomes also suggests a previously unappreciated complexity for fine-tuning of Shh-mediated gradients and pattern formation.</p>
},
	keywords = {Animals, Chick Embryo, Exosomes, Extracellular Space, Hedgehog Proteins, HEK293 Cells, Humans, MicroRNAs, Models, Biological, Protein Transport, Signal Transduction, Vertebrates},
	issn = {2045-2322},
	doi = {10.1038/srep07357},
	author = {Vyas, Neha and Walvekar, Ankita and Tate, Dhananjay and Lakshmanan, Vairavan and Bansal, Dhiru and Lo Cicero, Alessandra and Raposo, Graca and Palakodeti, Dasaradhi and Dhawan, Jyotsna}
}
