Metabolomics of Neural Progenitor Cells: A Novel Approach to Biomarker Discovery

Abstract

Finding biomarkers of human neurological diseases is one of the most pressing goals of modern medicine. Most neurological disorders are recognized too late because of the lack of biomarkers that can identify early pathological processes in the living brain. Late diagnosis leads to late therapy and poor prognosis. Therefore, during the past decade, a major endeavor of clinical investigations in neurology has been the search for diagnostic and prognostic biomarkers of brain disease. Recently, a new field of metabolomics has emerged, aiming to investigate metabolites within the cell/tissue/organism as possible biomarkers. Similarly to other “omics” fields, metabolomics offers substantial information about the status of the organism at a given time point. However, metabolomics also provides functional insight into the biochemical status of a tissue, which results from the environmental effects on its genome background. Recently, we have adopted metabolomics techniques to develop an approach that combines both in vitro analysis of cellular samples and in vivo analysis of the mammalian brain. Using proton magnetic resonance spectroscopy, we have discovered a metabolic biomarker of neural stem/progenitor cells (NPCs) that allows the analysis of these cells in the live human brain. We have developed signal-processing algorithms that can detect metabolites present at very low concentration in the live human brain and can indicate possible pathways impaired in specific diseases. Herein, we present our strategy for both cellular and systems metabolomics, based on an integrative processing of the spectroscopy data that uses analytical tools from both metabolomic and spectroscopy fields. As an example of biomarker discovery using our approach, we present new data and discuss our previous findings on the NPC biomarker. Our studies link systems and cellular neuroscience through the functions of specific metabolites. Therefore, they provide a functional insight into the brain, which might eventually lead to discoveries of clinically useful biomarkers of the disease.

Brain Maturation in Neonatal Rodents Is Impeded by Sevoflurane Anesthesia

“…Since previous studies have demonstrated a possible association of mobile lipids with apoptosis, 42–44 neuronal loss, and/or neuronal stem cell generation, 45,46 we were also interested in exploring whether there were changes in mobile lipids resonating at ≈1.30ppm and/or 0.9ppm in the sevoflurane-exposed rat pups. The spectral signature at 1.30ppm (represented by [Lip13a]) showed that there was a trend towards increase in the exposed group, particularly on PND8; however, this difference was not statistically significant (p>0.05, results not shown).…”

A metabolomics approach using juvenile cystic mice to identify urinary biomarkers and altered pathways in polycystic kidney disease

“…It is becoming increasingly clear, from work in our (18,21,37) and others' (20,24,27,28,46) laboratories, that metabolomics possesses significant as yet untapped potential for biomarker discovery, since it represents the signature of the actual processes that are occurring within the body rather than compounds (such as untranscribed DNA or pre-or posttranslationally modified proteins) that may be superfluous to these processes. In addition, there are a relatively small number of metabolites to examine compared with genes, transcripts, and proteins in their respective "omics" fields.…”

Transcriptional and Genomic Targets of Neural Stem Cells for Functional Recovery after Hemorrhagic Stroke

“…By using proton magnetic resonance spectroscopy, Maletić-Savatić et al discovered a metabolic biomarker of NSCs for the analysis in the live human brain, which connected systems with cellular neurobiology through the uses of certain specific metabolites. Thus, they give a functional observation into the living human brain, which may pave the way to the eventual discoveries of useful biomarkers of the diseases in clinic [75]. …”