Scientist unlock the secrets of what human cells really look like

Researchers are closer to answering the surprisingly complicated question, ‘what does a cell look like?’ after working with 200,000 images of stem cells of various sizes and shapes.

Although most of us would have seen a diagram of a mammal or plant, usually these designs are no more than rough descriptions, not actually how the cell’s organelles and interior would be organised.

And even within just one type of cell – for example a human induced pluripotent stem cell – there can be a huge variation.

“The way cells are organized tells us something about their behaviour and identity,” said one of the researchers, Allen Institute for Cell Science deputy director Susanne Rafelski.

“What’s been missing from the field, as we all try to understand how cells change in health and disease, is a rigorous way to deal with this kind of organisation.”

To understand how cells organise their interiors – what they looked like inside – the team started a collection of stem cells genetically engineered to light up 25 different internal structures and organelles under a fluorescent microscope. They then took 3D images of more than 200,000 different cells.

Even though the cells under study were genetically identical and reared in the same laboratory environment, their shapes varied substantially – some were long and pear-shaped, while others were short and blobby or a myriad of shapes in between.

By using mathematical frameworks, the team developed a ‘shape space’ that describes what the stem cell looked like on the outside. These were basic characterisations like height and volume, but also ‘pear-ness’ and ‘bean-ness’.

Only then could the researchers look at the cellular and organelle structure of similarly shaped cells – comparing pears to pears!

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Looking at the 25 organelles they found that within the groups with similar shapes the internal structure was incredibly similar.

“We know that in biology, shape and function are interrelated, and understanding cell shape is important to understand how the cells function,” said Matheus Viana, Allen Institute for Cell Science senior scientist.

“We’ve come up with a framework that allows us to measure a cell’s shape, and the moment you do that you can find cells that are similar shapes, and for those cells you can then look inside and see how everything is arranged.”

As well as giving scientists a much better understanding of how stem cells are put together, the researchers are hoping that it will allow scientists to look out for interesting deviations in the ‘normal’ cell structure – for example when the cell is dividing into two.

The research has been published in Nature.

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