Our paper on extracellular matrix networks and stem cell growth makes the cover of this week’s issue of the Journal of Biological Chemistry. The stunning image by Despina Soteriou captures stem cells growing in a web of extracellular matrix.

Journal of Biological Chemistry cover, 2013, vol. 288 (no. 26) // Image by Despina Soteriou

Journal of Biological Chemistry cover, 2013, vol. 288 (no. 26)

Stem cells interact with their microenvironment, and these interactions can influence the fate of the stem cells, directing them to differentiate into more specialised cells. To understand this phenomenon, Despina (who is co-first author of the article published today in the JBC) used fluorescence microscopy to image human embryonic stem cells as they grew on other cells – so-called feeder cells – which support the growth and self-renewal of stem cells.

Stem cells have great potential as therapeutic agents for the treatment of many diseases.

In the image, DNA in the cell nuclei is visible in blue, and pluripotent stem cells (which have the potential to produce different, specialised cell types) are marked by a transcription factor called Oct4, shown in red. Both DNA and Oct4 are usually found in cell nuclei, so their overlap appears purple in the image.

The striking stringy structure in green is the extracellular matrix molecule fibulin-2, which formed a web-like fibrillar network around the stem cell colonies.

It was clear from this and similar images that stem cells could interact intimately with the surrounding extracellular matrix microenvironment. But not all microenvironments are able to support the growth and self-renewal of pluripotent stem cells. This motivated us to investigate how different compositions of extracellular matrix could control the fate of a stem cell.

To begin to understand this, we used proteomics to compare the proteins in extracellular matrices that either could or could not support the growth of pluripotent stem cells. (I wrote about this work recently.) We identified several extracellular matrix molecules that could facilitate stem cell self-renewal. We also found that the right molecules must work together, like an interconnected web surrounding the stem cells, to control their fate effectively. Interestingly, our images of stem cells obtained by microscopy (such as Despina’s cover image, above), hint at exactly this idea, too.

Stem cells have great potential as therapeutic agents for the treatment of many diseases. Improved understanding of stem cell growth will enable scientists to develop new methods for cell-based therapies, and ultimately tissue regeneration, for the treatment of patients.

Funding: This work was supported by the Biotechnology and Biological Sciences Research Council, the Northwest Regional Development Agency, the Wellcome Trust and the Republic of Turkey Ministry of National Education.

Citation: D Soteriou, B Iskender, A Byron, JD Humphries, S Borg-Bartolo, M-C Haddock, MA Baxter, D Knight, MJ Humphries, SJ Kimber, Comparative proteomic analysis of supportive and unsupportive extracellular matrix substrates for human embryonic stem cell maintenance. J. Biol. Chem. 288, 18716–18731 (2013). HTML | PDF | PubMed