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 different sizes and shapes.
Although most of us have seen a diagram of a mammal or plant, these drawings are usually only rough descriptions, not how the organelles and cell interior would be arranged.
And even within a single cell type – for example a human-induced pluripotent stem cell – there can be enormous variation.
“The way cells are organized tells us something about their behavior and identity,” said one of the researchers, Susanne Rafelski, deputy director of the Allen Institute for Cell Science.
“What was missing in the field, as we all try to figure out how cells change in health and disease, is a rigorous way to manage this kind of organization.”
To understand how cells organize their interiors — what they looked like on the inside — the team started a collection of stem cells genetically engineered to illuminate 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 studied were genetically identical and raised in the same laboratory environment, their shapes varied widely – some were long and pear-shaped, while others were short and spotted or a myriad of shapes in between.
Using mathematical frameworks, the team developed a ‘shape space’ that describes what the stem cell looked like on the outside. These were basic characterizations like height and volume, but also the “pear” and the “bean”.
Only then were the researchers able to examine the cellular and organelle structure of similarly shaped cells – comparing pears to pears!
By examining the 25 organelles, they found that within the groups of similar shapes, the internal structure was incredibly similar.
“We know that in biology, form and function are interrelated, and understanding the shape of cells is important to understanding how they work,” said Matheus Viana, principal investigator at the Allen Institute for Cell Science.
“We’ve come up with a framework that allows us to measure the shape of a cell, and as soon as you do that, you can find cells that have similar shapes, and for those cells, you can then look at the interior and see how everything is arranged.”
As well as giving scientists a much better understanding of how stem cells are assembled, the researchers hope it will allow scientists to look for interesting deviations in “normal” cell structure, such as when the cell splits in two. .
The research has been published in Nature.