The role of biological gene expression noise during cellular differentiation

Grün Lab

A specific focus of the lab is the role of gene expression variability across single cells during differentiation (Grün et al., Nature Methods, 2014; Grün, Nature Methods, 2020). It has been shown that transcription is frequently not a continuous process but occurs in bursts. This induces substantial cell-to-cell variability of mRNA levels, and the role of this so-called biological noise during cellular differentiation is not well understood (Figure 1).

Figure 1 Genes can be transcribed in bursts leading to substantial variability across cells. This variability can be investigated with single cell sequencing or imaging based techniques to derive models for the regulation of gene expression noise. — **Figure 1** Genes can be transcribed in bursts leading to substantial variability across cells. This variability can be investigated with single cell sequencing or imaging based techniques to derive models for the regulation of gene expression noise.

© Dominic Grün

**Figure 1** Genes can be transcribed in bursts leading to substantial variability across cells. This variability can be investigated with single cell sequencing or imaging based techniques to derive models for the regulation of gene expression noise.

© Dominic Grün

Using single cell transcriptomics in conjunction with population based assays we try to elucidate how biological gene expression noise changes during differentiation and how it is mechanistically regulated. Since single cell sequencing still suffers from substantial technical noise we also utilize microscopic imaging of individual mRNAs in single cells (single molecule FISH) to investigate gene expression variability with high specificity and sensitivity.