Immunology, one cell at a time

Amir Giladi and Ido Amit in Nature:

CellFor more than a century, scientists have tried to characterize the different functions of the 10 trillion to 50 trillion cells of the human body — from neurons, which can reach 1 metre in length, to red blood cells, which are around 8 micrometres wide. Such efforts have helped to identify important cell types and pathways that are involved in human physiology and pathology. But it has become apparent that the research tools of the past few decades fail to capture the full complexity of cell diversity and function. (These tools include fluorescent tags fused to antibodies that bind to specific proteins on the surfaces of cells, known as cell-surface markers, and sequencing in bulk of the RNA or DNA of thousands of seemingly identical cells.) This failure is partly because many cells with completely different functions have similar shapes or produce the same markers. Single-cell genomics is transforming the ability of biologists to characterize cells. The new techniques that have emerged aim to capture individual cells and determine the sequences of the molecules of RNA and DNA that they contain. The shift in approach is akin to the change in how cells and molecules could be viewed during the 1980s, following advances in microscopy and the tagging and sorting of cells.

In the past five years, several groups of biologists, including our own laboratory, have gone from measuring the expression of a few genes in a handful of cells to surveying thousands of genes in hundreds of thousands of cells from intact tissues. New cell types1, 2, cellular states and pathways are being uncovered regularly as a result. Our lab was one of the first to study the immune system using single-cell genomics. The tools are particularly suited to this task because the heterogeneity and plasticity of cells are integral to how the immune system works — the nature of each agent that could attack the body being impossible to know ahead of time.

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