Compared to hematopoietic stem cells (HSCs) isolated from adults, HSCs isolated from cord blood (CB) have enhanced proliferative potential and can lead to hematological reconstitution when engrafted in children with hematological malignancies or genetic defects.
Unfortunately, small numbers of HSCs are present in single CB collections, limiting their use as grafts for adults. For several decades investigators have used a variety of strategies to expand the numbers of CB HSC ex vivo with limited success.
Evidence indicates that accumulation of epigenetic modifications influences preservation of stem cell characteristics in HSC daughter cells; therefore, in this issue of the Journal of Clinical Investigation, Pratima Chaurasia and colleagues at Mount Sinai School of Medicine expanded CB HSCs in the presence of histone deacetylase inhibitors (HDACIs) and evaluated their characteristics. Valproic acid (VPA)-treated CB HSCs produced greater numbers of HSCs that expressed several pluripotency genes.
Compared to conventionally expanded CB HSCs, VPA-treated HSCs were more efficient in repopulating the bone marrow and establishing hematopoietic populations in immune deficient mice. In an accompanying Commentary, Hal Broxmeyer of the Indiana University School of Medicine discusses how these findings enhance our understanding of HSC function and could provide clinical benefit.
Epigenetic reprogramming induces the expansion of cord blood stem cells Ronald Hoffman Pratima Chaurasia http://www.jci.org/articles/view/70313
Receptors in the brain mediate the weight loss effects of GLP1 agonists
Glucagon-like peptide-1 (GLP1) analogs are able to achieve both weight loss and glucose tolerance, both of which are crucial for controlling type 2 diabetes (T2D).
GLP1 receptors (GLP1Rs) are present in the brain, but it is not clear if the brain does indeed mediate the weight loss and glucose lowering effects of GLP1 analogs. In this issue of the Journal of Clinical Investigation, Stephanie Sisley and colleagues at Cincinnati Children's Hospital Medical Center evaluated the effects of the GLP1 agonist liraglutide in animals lacking GLP1R in the central nervous system (CNS) or in visceral nerves and found that liraglutide had no effect on weight loss or food intake in these animals, even those fed a high fat diet.
Interestingly, liragludtie administration did lower glucose levels in animals lacking GLP1R in either the CNS or visceral nerves. Together, these data indicate that neuronal GLP1Rs mediate weight loss and anorectic effects, but do not mediate glucose lowering.
TITLE: Neuronal GLP1R mediates liraglutide's anorectic but not glucose-lowering effect Stephanie Sisley http://www.jci.org/articles/view/72434