Memory and relatedness of transcriptional activity in mammalian cell lineages

• Published in: Nature communications Vol. 10; no. 1; p. 1208
• Main Authors: Phillips, Nicholas E., Mandic, Aleksandra, Omidi, Saeed, Naef, Felix, Suter, David M.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 14.03.2019; Nature Publishing Group; Nature Portfolio
• Subjects: 14/5; 14/63; 38; 38/44; 631/114/2397; 631/208/199; 631/80/2373; Animals; Cell Line; Cell Lineage - genetics; Embryo cells; Gene expression; Gene Expression Regulation - genetics; Genes; HEK293 Cells; Heterogeneity; Humanities and Social Sciences; Humans; Intravital Microscopy; Mammalian cells; Mammals; Mathematical models; Mice; Microscopy, Fluorescence; Models, Biological; Mouse Embryonic Stem Cells; multidisciplinary; Science; Science (multidisciplinary); Single-Cell Analysis; Stem cell transplantation; Stem cells; Time-Lapse Imaging; Transcription; Transcription Factors - metabolism; Transcription, Genetic
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-019-09189-8

Phenotypically identical mammalian cells often display considerable variability in transcript levels of individual genes. How transcriptional activity propagates in cell lineages, and how this varies across genes is poorly understood. Here we combine live-cell imaging of short-lived transcriptional reporters in mouse embryonic stem cells with mathematical modelling to quantify the propagation of transcriptional activity over time and across cell generations in phenotypically homogenous cells. In sister cells we find mean transcriptional activity to be strongly correlated and transcriptional dynamics tend to be synchronous; both features control how quickly transcriptional levels in sister cells diverge in a gene-specific manner. Moreover, mean transcriptional activity is transmitted from mother to daughter cells, leading to multi-generational transcriptional memory and causing inter-family heterogeneity in gene expression. Phenotypically identical mammalian cells often display considerable variability in transcript levels of individual genes. Here the authors document how different genes propagate their expression levels in cell lineages and suggest a potential role of transcriptional memory for generating spatial patterns of gene expression.