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Ultrasensitive Mass Spectrometry for Deciphering Cell Heterogeneity

Speaker: Peter Nemes, Associate Professor, Department of Chemistry & Biochemistry, University of Maryland-College Park Location: 402 N Blackford St. Indianapolis, IN 46202 LD 010

Host: Manicke

​Formation of cell-to-cell differences (cell heterogeneity) is critical to normal patterning of the embryonic body and development of the central nervous system, but how functionally important proteins and small molecules underlie cell heterogeneity in the vertebrate embryo is little understood. The challenge has been mass spectrometry (MS) characterization of low signal intensities that are yielded by miniscule amounts of proteins and metabolites contained by single cells. While the classical approach to combine multiple cells certainly enhances detection sensitivity, cell pooling averages out signals across cells, losing potentially important cell-specific molecular events, such as those responsible for inducing differential cell fates during early embryogenesis or establishment of neuron heterogeneity. In this presentation, we will discuss ultrasensitive microanalytical MS platforms that we have recently developed to enable the detection and quantification of hundreds-to-thousands of proteins and hundreds of metabolite signals in single embryonic cells in the early developing embryo of the South African clawed frog (Xenopus laevis), a powerful model in cell and developmental biology. We will also provide vignettes on how we use these single-cell mass spectrometers to uncover previously unknown proteomic and metabolic cell heterogeneity in the 4-to-128-cell embryo, discover molecules that can alter the normal tissue fate of embryonic cells, and how these results can be leveraged to formulate new hypotheses regarding the functional significance of proteins or metabolites during early embryogenesis. Last, we will discuss technological developments toward enabling the study of gene translation from small populations of mammalian neurons in the mouse cortex. Single-cell MS is flexible to characterizing cellular events downstream of gene transcription, viz. at the levels of proteins and metabolites, thus opening exciting new research potentials in basic and translational research.