Cell Division Is More Asymmetrical Than Previously Thought

Scientists from The University of Manchester have changed our understanding  of how cells in living organisms divide, which could revise what students are taught at school.

In a Wellcome funded study published today (01/05/25) in Science - one of the world’s leading scientific journals – the researchers challenge conventional wisdom taught in schools for over 100 years.

Students are currently taught that during cell division, a ‘parent’ cell will become spherical before splitting into two ‘daughter’ cells of equal size and shape.

However, the study reveals that cell rounding is not a universal feature of cell division and is not how it often works in the body.

Dividing cells, they show, often don’t round up into sphere-like shapes. This lack of rounding breaks the symmetry of division to generate two daughter cells that differ from each other in both size and function, known as asymmetric division.

Asymmetric divisions are an important way that the different types of cells in the body are generated, to make different tissues and organs.

Until now, asymmetric cell division has predominantly only been associated with highly specialised cells, known as stem cells.

The scientists found that it is the shape of a parent cell before it even divides that can determine if they will round or not in division and determines how symmetric, or not, its daughter cells are going to be.

Cells which are shorter and wider in shape tend to round up and divide into two cells which are similar to each other.  However, cells which are longer and thinner don’t round up and divide asymmetrically, so that one daughter is different to the other.

The findings could have far reaching implications on our understanding of the role of cell division in disease. For example, in the context of cancer cells, this type of ‘non-round’, asymmetric division could generate different cell behaviours known to promote cancer progression through metastasis.

Harnessing this information could also impact regenerative medicine, enabling us to better manufacture the cell types needed to regenerate damaged tissues and organs.

Scientists may one day be able to influence the function of daughter cells by simply manipulating their parental cell shape.

Co-lead author Dr Shane Herbert, a senior research fellow at The University of Manchester said: “The phenomenon of mitosis - or cell division - is one of the fundamentals of life and a basic biological concept which is taught from school age.

“Students learn that when a cell divides, it will generate a uniform spherical shape. Our study, however, shows that in real living organisms, it is not as simple as that.

“Our research suggests that the shape of the cell before it divides can fundamentally direct whether a cell rounds, and importantly, if its daughters are symmetric or asymmetric both in size and function.”

The scientists used real time imaging to study the formation of blood vessels in 1-day old transparent zebrafish embryos.

Growing blood vessels and other tissues are made of strands of collectively migrating cells.

Each new vessel is led by a special fast-moving cell at the front with slower cells following behind.

When the fast moving “tip” cell divided, the study showed, it didn’t “round-up” as expected. In doing so it was able to divide asymmetrically and generate the new fast “tip” cell at the front and a slower following cell behind it.

Co-lead author Dr Holly Lovegrove, a lecturer at The University of Manchester said: “Using transparent 1-day old zebrafish embryos allows us to study a dynamic process like cell division inside a living organism.

“We are therefore able to make movies of this fundamental cell behaviour and in doing so reveal exciting new aspects of how tissues grow.”

The team also used a technique using human cells called micropatterning.

Co-First author Dr Georgia Hulmes, a Postdoctoral Research Associate at The University of Manchester said: “Micropatterning allows us to generate specifically shaped microscopic patches of proteins that cells can stick to.

“The cells will then take the shape of the patch. This therefore allows us to change the shape of the cells and test how these shapes impact on the subsequent cell division.”

The micropatterning system used by the scientists is called PRIMO by Alvéole. This system allowed the scientists  to manipulate cells into different shapes at tiny resolutions of less than a tenth of the width of a human hair. A UV laser is used to burn specific shapes onto a non-sticky surface. Cells are then seeded onto the surface and will only be able to stick down in areas where the UV laser has printed a shape. The cells then spread out into the laser patterned shape and this allowed the scientists to create the precise shape of cell they desire.

Reference: Lovegrove HE, Hulmes GE, Ghadaouia S, et al. Interphase cell morphology defines the mode, symmetry, and outcome of mitosis. Science. 2025;388(6746):eadu9628. doi: 10.1126/science.adu9628

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