Pedro Aragon Fernandez
Pedro Aragón holds a bachelor’s and master’s degree in biochemistry from the Technical University of Munich (TUM). He developed an interest in analytical chemistry for biological applications and continued to pursue a PhD in the Cell Diversity Lab supervised by Prof. Erwin M. Schoof at the Technical University of Denmark (DTU). His current work focuses on the development and implementation of novel preparative and analytical strategies for mass spectrometry-based single-cell proteomics to understand the synergy displayed by phenotypically distinct subpopulations in the hematopoietic system.
Sessions
In the era of single-cell screenings, RNA-based technologies have been the gold standard for the systematic study of cell state heterogeneity and differentiation dynamics of complex cellular systems. Recently, single-cell proteomics by mass spectrometry (scp-MS) has reached a maturity level where it can reliably measure the proteomes of thousands of individual cells in an unbiased manner.
Here, we leverage these technological advances for the characterization of a primary acute myeloid leukemia (AML) sample obtained from a relapsed patient. Our analysis not only recapitulates the known hierarchical cellular composition observed in AML but suggest a new non-canonical differentiation avenue through which quiescent leukemic stem cells are able to reconstitute the terminal CD15+CD14+ blast pool, recognized as the main effectors of the disease and targets of commonly used therapeutics.
Through trajectory analysis, we show several key proteins exhibiting an asynergic expression profile across the developmental bifurcation leading to a heterogeneous blast reservoir not previously observed by measurements of mRNA transcripts alone.
In summary, in this work we demonstrate the capability of scp-MS to interrogate complex biological systems at single cell resolution. We hypothesize a new developmental model in AML awaiting further experimental validation and underline the potential towards integrative analysis employing different modalities of biological information in combination with scpMS.