An analysis of the time course of attention in preview search.

We used a probe dot procedure to examine the time course of attention in preview search (Watson and Humphreys, 1997). Participants searched for an outline red vertical bar among other new red horizontal bars and old green vertical bars, superimposed on a blue background grid. Following the reaction time response for search, the participants had to decide whether a probe dot had briefly been presented. Previews appeared for 1,000 msec and were immediately followed by search displays. In Experiment 1, we demonstrated a standard preview benefit relative to a conjunction search baseline. In Experiment 2, search was combined with the probe task. Probes were more difficult to detect when they were presented 1,200 msec, relative to 800 msec, after the preview, but at both intervals detection of probes at the locations of old distractors was harder than detection on new distractors or at neutral locations. Experiment 3A demonstrated that there was no difference in the detection of probes at old, neutral, and new locations when probe detection was the primary task and there was also no difference when all of the shapes appeared simultaneously in conjunction search (Experiment 3B). In a final experiment (Experiment 4), we demonstrated that detection on old items was facilitated (relative to neutral locations and probes at the locations of new distractors) when the probes appeared 200 msec after previews, whereas there was worse detection on old items when the probes followed 800 msec after previews. We discuss the results in terms of visual marking and attention capture processes in visual search

Heterogeneous bone-marrow stromal progenitors drive myelofibrosis via a druggable alarmin axis

Functional contributions of individual cellular components of the bone-marrow microenvironment to myelofibrosis (MF) in patients with myeloproliferative neoplasms (MPNs) are incompletely understood. We aimed to generate a comprehensive map of the stroma in MPNs/MFs on a single-cell level in murine models and patient samples. Our analysis revealed two distinct mesenchymal stromal cell (MSC) subsets as pro-fibrotic cells. MSCs were functionally reprogrammed in a stage-dependent manner with loss of their progenitor status and initiation of differentiation in the pre-fibrotic and acquisition of a pro-fibrotic and inflammatory phenotype in the fibrotic stage. The expression of the alarmin complex S100A8/S100A9 in MSC marked disease progression toward the fibrotic phase in murine models and in patient stroma and plasma. Tasquinimod, a small-molecule inhibiting S100A8/S100A9 signaling, significantly ameliorated the MPN phenotype and fibrosis in JAK2V617F-mutated murine models, highlighting that S100A8/S100A9 is an attractive therapeutic target in MPNs.Leimkühler and colleagues demonstrate that mesenchymal stromal progenitor cells are fibro

Heterogeneous bone-marrow stromal progenitors drive myelofibrosis via a druggable alarmin axis

Summary Functional contributions of individual cellular components of the bone-marrow microenvironment to myelofibrosis (MF) in patients with myeloproliferative neoplasms (MPNs) are incompletely understood. We aimed to generate a comprehensive map of the stroma in MPNs/MFs on a single-cell level in murine models and patient samples. Our analysis revealed two distinct mesenchymal stromal cell (MSC) subsets as pro-fibrotic cells. MSCs were functionally reprogrammed in a stage-dependent manner with loss of their progenitor status and initiation of differentiation in the pre-fibrotic and acquisition of a pro-fibrotic and inflammatory phenotype in the fibrotic stage. The expression of the alarmin complex S100A8/S100A9 in MSC marked disease progression toward the fibrotic phase in murine models and in patient stroma and plasma. Tasquinimod, a small-molecule inhibiting S100A8/S100A9 signaling, significantly ameliorated the MPN phenotype and fibrosis in JAK2V617F-mutated murine models, highlighting that S100A8/S100A9 is an attractive therapeutic target in MPNs

Single-cell analysis of cultured bone marrow stromal cells reveals high similarity to fibroblasts in situ

Within the heterogenous pool of bone marrow stromal cells, mesenchymal stromal cells (MSCs) are of particular interest because of their hematopoiesis-supporting capacities, contribution to disease progression, therapy resistance, and leukemic initiation. Cultured bone marrow-derived stromal cells (cBMSCs) are used for in vitro modeling of hematopoiesis–stroma interactions, validation of disease mechanisms, and screening for therapeutic targets. Here, we place cBMSCs (mouse and human) in a bone marrow tissue context by systematically comparing the transcriptome of plastic-adherent cells on a single-cell level with in vivo counterparts. Cultured BMSCs encompass a rather homogenous cell population, independent of the isolation method used and, although still possessing hematopoiesis-supporting capacity, are distinct from freshly isolated MSCs and more akin to in vivo fibroblast populations