Genetic noise shown to influence cells' decisions

Although different cell types have unique roles, they all start out the same. New research has found that random differences between cells early in development could be the key to making different cells in the body.

A team of researchers from Babraham Institute, EMBL-EBI, and the Wellcome Trust-Medical Research Council Stem Cell Institute examined stem cells from embryos at the earliest stages of development. Typically, cells of the same type have matching patterns of gene activity—many of the same genes are turned off or on in all cells. In this research, published today in Cell Reports, it was revealed that when cells start specializing into different cell types their gene activity becomes more “noisy” —each cell starts to turn different groups of genes on or off.

Specifically when cells are making decisions about what to become, there is greater variation in the activity of the genes in different cells—the same genes may be turned on in some cells and off in others. By chance this noise will make some cells more likely to become one type of cell, while others will start to favor an alternative.

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According to Hisham Mohammed of the Babraham Institute, and one of the paper's co-first authors, "Our analyses suggest that elevated transcriptional noise at two key points in early development coincides with cell fate decisions. By contrast, after these decisions cells become highly synchronized and grow rapidly. Our study systematically charts transcriptional noise and uncovers new processes associated with early lineage decisions."

Single-cell sequencing was used in this study to great effect. According to the team, previous research has only examined groups of cells. Co-senior author, professor Jennifer Nichols at the Wellcome Trust, said: "Our data allow us to study gene activity in individual cells to an unprecedented level of precision. This detail has allowed us to observe substantial differences between cells. Regulating noisy gene activity during development may be a key part of how cells make decisions about their future. In the future we hope to discover how this process is controlled to better understand how noise shapes early development."

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