Genetic Basis for Gray Platelet Syndrome
Hospital for Sick Children ♦ University of Toronto ♦ University of Colorado ♦ University of Utah ♦ Others..
Published in Nature Genetics, July 17, 2011
Researchers have found a mutation in the gene NBEAL2 which seems to be at the root of Gray Platelet Syndrome (GPS), a disorder characterized by thrombocytopenia and enlarged platelets that lack α-granules. The discovery was enabled by RNA sequence analysis of platelets taken from an individual with autosomal recessive GPS. The mutation prevents recognition of a splice site at exon 9 in the mRNA strand encoding the protein neurobeachin-2. As a result of intron retention, premature stop codons are introduced to the mRNA strand; stop codons are known to cause mRNA degradation or protein truncation. Neurobeachin-2 contains a BEACH domain that is thought to be involved in cellular trafficking, and a defect in this protein likely leads to the manifestation of GPS.
Cell Fate Potential is Primed by Histones
McMaster University ♦ Published in Cell Stem Cell, July 8, 2011
Mick Bhatia’s lab has dug a little deeper into the mechanisms that bias lineage specification and differentiation of human embryonic stem cells (hESCs). Historically, it has been assumed that human embryonic stem cells are “equipotent”, meaning each and every one has the same potential, or equal potential, to differentiate into any of the more than 225 cell types in the human body. This theory has evolved over the last few years, and these recent findings confirm that the scene is quite a bit more colourful than originally thought. Embryonic stem cells are in fact restricted to certain lineages and this restriction is encoded by histone modification and patterning. Researchers in Bhatia’s lab illustrate this by fractionating stem cells in culture based on two surface markers, c-KIT and A2B5, and predicting cell fate based on histone modification marks observed on gene loci associated with pluripotency or various lineages.
Sorting with CD49f Provides Highest Reported Purity of HSCs
Campbell Family Institute for Cancer Research ♦ Ontario Cancer Institute ♦ University of Toronto
Published in Science ♦ July 8, 2011
Purification of specific cell types is essential to their study in vitro. Hematopoietic stem cells (HSCs), rare and quiescent cells that gives birth to all blood and immune cells in the bone marrow compartment, are under investigation for use in cell therapies and other regenerative medicine applications. Although fractions of cells can be enriched containing HSCs, all too often these subsets contain contaminating cell types that are not true stem cells. Lineage-restricted multipotent progenitors, for example, express the surface marker CD34, similar to HSCs, but do not exhibit the long-term multilineage graft potential that is indicative of a more primordial cell. Multiple markers have been analyzed at once in attempts to enrich solely for HSCs, but even these combinations, including CD38, Thy1, and CD45RA, are not adequate to do the trick. Researchers in John Dick’s lab have discovered a marker, CD45f, that seems to provide an even finer resolution while sorting for HSCs. Using flourescence-activated cell sorting, researchers enriched for a CD45f fraction and transplanted single cells into the femurs of mice. Many of these transplanted cells were capable of long-term multilineage engraftment. Sorting with CD45f allows for the highest purity of HSCs ever reported in the literature, coming in at around 9.5%.