Deciphering Metabolic Heterogeneity by Single-Cell Analysis

Abstract

Single-cell analysis provides insights into cellular heterogeneity and dynamics of individual cells. This Feature highlights recent developments in key analytical techniques suited for single-cell metabolic analysis with a special focus on mass spectrometry-based analytical platforms and RNA-seq as well as imaging techniques that reveal stochasticity in metabolism.

Fig. 1:. Single-cell transcriptome analyses of tissues and cell types.

Reproduced with permission from ref Copyright (2014) Springer Nature.

Fig. 2:. Common mass spectrometric techniques in single-cell metabolic analysis.

Working principles of MALDI (a), DESI (b) and SIMS (c), their beam diameters (d), mass detection ranges (e) and sample preparation times (f). Reproduced with permission from ref Copyright (2018) ROYAL SOCIETY OF CHEMISTRY.

Fig. 3.. Following metabolic fluctuations in time.

Individual cells display gene expression and growth rates that vary strongly in time, in a correlated fashion, by at least two different mechanisms: a) Fluctuations in the expression of limiting metabolic enzymes lead to metabolic fluxes that vary in time, which in turn cause delayed growth rate fluctuations. Adapted with permission from ref Copyright (2014) Springer Nature b) Expression itself is also affected by metabolic fluctuations, possibly mediated by varying levels of amino acids or ATP. This mechanism also generates correlations in expression and growth fluctuations, but without the time delays seen in panel a. Adapted with permission from ref Copyright (2018) Elsevier.