Most of us are at least somewhat curious about our lineage: are we descended from a king, an outlaw, or maybe just a particularly snazzy dresser? And do our distant cousins in faraway lands share certain characteristics (such as a penchant for polyester) with us? A group of researchers in Norway asked similar questions about mesenchymal stem cells (MSCs) in various tissues—where did they come from, and how are they related?
MSCs isolated from bone marrow, skeletal muscle, and adipose tissues have similar characteristics, and some evidence suggests a common origin from multipotent cells (called pericytes) that line blood vessels. When the researchers analyzed genome-wide promoter DNA methylation patterns of MSCs from bone marrow, skeletal muscle, and adipose tissue, they found that:
- Promoter DNA methylation patterns overlapped for MSCs isolated from the three tissues. On the other hand, bone-marrow-derived hematopoietic progenitors were more distantly related from an epigenetic standpoint.
- Genes associated with early development were hypermethylated and repressed in MSCs.
- Most lineage-specification promoters were hypomethylated and had both transcriptionally permissive and repressive histone modifications. This “potentially permissive” state might prime MSCs for differentiation, during which the repressive mark is lost in expressed genes and retained in silenced genes.
So what does this all mean to an MSC searching for its roots? The researchers say that their results support a common origin of mesenchymal progenitors, and that promoter methylation patterns of differentiated cells are established primarily at the progenitor stage. Untangle the branches of the MSC family tree for yourself at Molecular Biology of the Cell, April 2010.