Stem cells have the amazing capacity to develop into different types of cells in the body, which is essential for the development of an embryo, for example. Stem cells also have the ability to renew themselves, dividing to replenish other cells and to replace damaged tissue.

Their remarkable regenerative properties offer hope for new treatments for disease

The proteins and sugars that surround cells – the extracellular matrix – are very important to hold cells in place, allow cells to move, and relay communication signals to and from cells. This is certainly the case for stem cells.

The extracellular matrix is critical for stem cells to function properly.

Stem cells can sense the stiffness of the extracellular matrix scaffold surrounding them. It turns out that this sensation of the local environment can determine the type of cells that the stem cells become.

For example, stiff extracellular matrix – like bone – influences stem cells to become bone cells. On the other hand, soft extracellular matrix can cause stem cells to become fat cells or nerve cells.

But how exactly do stem cells sense the extracellular matrix environment?

Integrin receptors on the cell surface sense the extracellular matrix // Image by Adam Byron

Integrin receptors on the cell surface sense the extracellular matrix

Proteins called integrins, which sit on the surface of cells, serve as sensors of the extracellular matrix. They respond to the cell’s surroundings by binding to lots of other proteins inside the cell, forming ‘adhesion complexes’. These clusters of proteins allow a cell to adhere to its surroundings and to transmit signals in and out of the cell, controlling its behaviour (like to where it moves or when it divides or, if it’s a stem cell, whether it renews itself).

Sensing of the extracellular matrix controls the fate of stem cells // Image by Adam Byron

Sensing of the extracellular matrix controls the fate of stem cells

The types of proteins that form adhesion complexes in stem cells are not well understood. These proteins are likely to be very important in allowing stem cells to sense their surroundings.

In work from the University of Manchesterpublished in the January issue of the journal Proteomics Clinical Applications, the proteins that form adhesion complexes in mesenchymal stem cells were catalogued. The clusters of proteins were isolated from cells and identified by proteomics, a technique that measures the type and number of proteins in a sample.

Many proteins were detected that link integrins on the surface of stem cells to the cellular skeleton (the ‘cytoskeleton’). Proteins known to cluster at adhesion complexes when cells sense the stiffness of the surroundings were also detected. These proteins, known as LIM domain proteins, are interesting because they help transmit cellular signals about extracellular matrix stiffness. So, these proteins may be important in determining which type of cell a stem cell becomes, depending on the cell’s surroundings.

The dataset of identified proteins – which is freely available to download – provides a useful resource of information about the collections of proteins that help stem cells sense their surroundings.

This will lead to a better understanding of stem cell biology, so that stem cells may be used as therapies to treat diseases in which sensing stem cells’ surroundings goes wrong.

Funding
This work was supported by the Wellcome Trust, BBSRC, North-west Regional Development Agency, Becas Chile and the University of Manchester.

Citation
Ajeian et al. Proteomic analysis of integrin-associated complexes from mesenchymal stem cells. Proteomics Clin. Appl. 10, 51–57 (2016)
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