The gift giving started bit early this year for the stem cell community as an international team of researchers shared key findings that could transform clinical applications of human blood stem cells. They wrapped up miR-126 binding sites in lentiviral vectors and put a serious smack down on miR-126 activity in hematopoietic stem cells (HSCs). They found that miR-126 puts the brakes on cell division in these cells, which could place limits on the amount of HSCs in the body.
The team from Canada, Italy, and Japan previously showed that miR-126 is highly expressed in mouse and human HSCs, and levels decrease with differentiation. In this more recent work that saw more gains/losses (of function) than the Dow Jones this year, they used lentiviral vectors to overexpress (OE) or knockdown (KD) miR-126.
They found that overexpressing miR-126 slowed down cell division, but knocking down miR-126 allowed HSCs to keep on dividing without “exhaustion.” The effect was most pronounced in early progenitor HSCs, so miR-126 likely functions to reduce proliferation in less differentiated (more “primitive”) cells.
miR-126 does its thing by regulating components of the PI3K/AKT pathway, setting a threshold for HSC activation and setting limits on the HSC pool size.
The study shows that lowering miR-126 levels expands the stem cells for long periods of time while keeping them in an early state, which could open up lots of therapeutic applications, they say.
Read all the details at Cell Stem Cell, December 2012.