Exploring cell heterogeneity in health and disease using single-cell proteomics and transcriptomics

Single-cell proteomics by Mass Spectrometry (scp-MS) can provide valuable insights into distinct cell-states and signalling patterns present in a cell population. However, carrying out proteomics profiling from the limited amount of material encapsulated in an individual cell presents significant challenges. Tremendous efforts have been made to optimize all aspects of scp-MS, with the aim of minimizing losses during sample preparation and maximizing sensitivity of data acquisition.

Here, we will present recent approaches developed in the Cell Diversity Lab. We will cover key aspects of the entire workflow and showcase the application of our methods to address biological questions spanning across stem cell differentiation, and especially Acute Myeloid Leukemia. With a particular focus on the healthy and malignant human blood system, we aim to convey possible bio- medical implications of scp-MS, and the joint assessment of transcriptomes and proteomes at the single-cell level. Through these examples, we provide an overview of the current technological state of the field and highlight key challenges that remain to be solved.