A Single-Cell Taxonomy Predicts Inflammatory Niche Remodeling to Drive Tissue Failure and Outcome in Human AML.

Unlabelled: Cancer initiation is orchestrated by an interplay between tumor-initiating cells and their stromal/immune environment. Here, by adapted single-cell RNA sequencing, we decipher the predicted signaling between tissue-resident hematopoietic stem/progenitor cells (HSPC) and their neoplastic counterparts with their native niches in the human bone marrow. LEPR+ stromal cells are identified as central regulators of hematopoiesis through predicted interactions with all cells in the marrow.

Hematopoietic Cell Autonomous Disruption of Hematopoiesis in a Germline Loss-of-function Mouse Model of -FPD.

familial platelet disorder (-FPD) is a hematopoietic disorder caused by germline loss-of-function mutations in the gene and characterized by thrombocytopathy, thrombocytopenia, and an increased risk of developing hematologic malignancies, mostly of myeloid origin. Disease pathophysiology has remained incompletely understood, in part because of a shortage of models recapitulating the germline loss of function found in humans, precluding the study of potential contributions of non-hematopoietic cells to disease pathogenesis. Here, we studied mice harboring a germline hypomorphic mutation of one allele with a loss-of-function mutation in the other allele ( mice), which display many hematologic characteristics found in human -FPD patients.

The mesenchymal niche in MDS.

Myelodysplastic syndrome (MDS) is characterized by bone marrow failure and a strong propensity for leukemic evolution. Somatic mutations are critical early drivers of the disorder, but the factors enabling the emergence, selection, and subsequent leukemic evolution of these "leukemia-poised" clones remain incompletely understood. Emerging data point at the mesenchymal niche as a critical contributor to disease initiation and evolution.

Systemic Virus Infections Differentially Modulate Cell Cycle State and Functionality of Long-Term Hematopoietic Stem Cells In Vivo.

Quiescent long-term hematopoietic stem cells (LT-HSCs) are efficiently activated by type I interferon (IFN-I). However, this effect remains poorly investigated in the context of IFN-I-inducing virus infections. Here we report that both vesicular stomatitis virus (VSV) and murine cytomegalovirus (MCMV) infection induce LT-HSC activation that substantially differs from the effects triggered upon injection of synthetic IFN-I-inducing agents.