Vascular niche E-selectin regulates hematopoietic stem cell dormancy, self renewal and chemoresistance
NATURE MEDICINE
Authors: Winkler, Ingrid G.; Barbier, Valerie; Nowlan, Bianca; Jacobsen, Rebecca N.; Forristal, Catherine E.; Patton, John T.; Magnani, John L.; Levesque, Jean-Pierre
Abstract
The microenvironment, or niche, surrounding a stem cell largely governs its cellular fate. Two anatomical niches for hematopoietic stem cells (HSCs) have been reported in the bone marrow, but a distinct function for each of these niches remains unclear. Here we report a new role for the adhesion molecule E-selectin expressed exclusively by bone marrow endothelial cells in the vascular HSC niche. HSC quiescence was enhanced and self-renewal potential was increased in E-selectin knockout (Sele(-/-)) mice or after administration of an E-selectin antagonist, demonstrating that E-selectin promotes HSC proliferation and is a crucial component of the vascular niche. These effects are not mediated by canonical E-selectin ligands. Deletion or blockade of E-selectin enhances HSC survival threefold to sixfold after treatment of mice with chemotherapeutic agents or irradiation and accelerates blood neutrophil recovery. As bone marrow suppression is a severe side effect of high-dose chemotherapy, transient blockade of E-selectin is potentially a promising treatment for the protection of HSCs during chemotherapy or irradiation.
Characterizing the Paleocene turbidites of the North Sea: the Mey Sandstone Member, Lista Formation, UK Central Graben
PETROLEUM GEOSCIENCE
Authors: Kilhams, Ben; Hartley, Adrian; Huuse, Mads; Davis, Chris
Abstract
This paper presents an integrated seismic, petrophysical and core facies study of the Mey Sandstone Member of the Central North Sea Lista Formation. Seismic mapping and attribute analysis reveal that the Mey Sandstone Member is composed of distinct axial and lateral routing systems. In turn, the axial system can be divided into coeval western and eastern fairways defined by the underlying graben topography in a similar manner to the overlying Sele Formation (Forties) sandstones. These trends are confirmed by petrophysical analysis, which also reveals that the lateral systems are not as important as previously proposed and that the cycles of the Mey Sandstone Member prograded over time before a late stage of backstepping. These variations can be related directly to published sea-level curves. Core analysis reveals that mean grain size is the main control on sandstone quality and that similar proximal (channelized) to distal (sheet-like) changes in sedimentological facies occur to those described in the Sele Formation. It is argued that these deposits cannot be described as simple basin floor fans due to the impact of topography on turbidite flow routing and the existence of multiple entry points of sediment into the basin.