Stem Cells and Their Fat Neighbors

We recently published a PLOS ONE paper (Mitochondrial respiration regulates adipogenic differentiation of human mesenchymal stem cells) in which we studied how the metabolism of an adult stem cell can influence its ability to differentiate. Human bone marrow mesenchymal stem cells (also known as marrow stromal cells, marrow progenitor cells or MSCs) can be converted into fat (adipocytes), cartilage (chondrocytes) or bone (osteoblasts). The work performed by Yanmin Zhang and Glenn Marsboom in my lab showed that MSCs undergo a major metabolic shift towards increased mitochondrial oxidation when they become fat cells and that suppressing mitochondrial respiration can prevent their differentiation. The metabolic state of the adult stem cells is therefore not only an indicator of their “stemness”, it can be used to either promote or suppress their differentiation.

 

Dr. Peter Toth, one of the co-authors on the paper, helped us acquire some really beautiful images of the cells that I would like to share with the readers of the blog. The image below shows undifferentiated adult human bone marrow mesenchymal stem cells (MSCs) that were exposed to an adipogenic differentiation medium, i.e a combination of factors which induces the formation of fat cells (adipocytes). However, as with many stem cell differentiation protocols, not all stem cells turned into fat cells. The cells on the right have a typical fat-like structure in which cells are full of round lipid droplets. The neighboring cells on the left are MSCs that have not (yet?) become fat cells. We stained the cells with the fluorescent mitochondrial dye JC-1. Depolarized mitochondria appear green and hyperpolarized mitochondria red. As you can see, the cells on the left have a much higher mitochondrial membrane potential (significant amount of red among the green mitochondria) than their fat neighbors on the right (mostly green mitochondria, all of them located between lipid droplets). By capturing both cell types next to each other, we could show an illustrative example of how entwined metabolism and stem cell differentiation are. The morphology and metabolic state of neighboring cells in this image were quite different, despite the fact that all cells were subjected to the same cocktail of differentiation factors. The blue-appearing dye is DAPI and stains nuclei of cells so one can tell the cells apart. Each cell in this image has one blue nucleus.

 

 

The image was published with a PLoS ONE CC-BY license. Feel free to use it as an example of adult stem cell differentiation or how mitochondrial morphology and function can vary between stem cell and its differentiated progeny, as long as you attribute the original PLoS One paper. The image in the paper also has a scale bar and asterisks/arrows pointing out the specific cells.

 

Zhang Y, Marsboom G, Toth PT, & Rehman J (2013). Mitochondrial respiration regulates adipogenic differentiation of human mesenchymal stem cells. PLoS ONE 8(10): e77077;  PMID: 24204740; DOI: 10.1371/journal.pone.0077077

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