Volume 5.37 | Sep 30

Hematopoiesis News 5.37 September 30, 2014
Hematopoiesis News
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N-Glycosylation Bidirectionally Extends the Boundaries of Thymocyte Positive Selection by Decoupling Lck from Ca2+ Signaling
During thymocyte development, N-glycan branching varied approximately 15-fold. N-glycan branching was required for positive selection and decoupled Lck signaling from T cell antigen receptor-driven Ca2+ flux to simultaneously promote low-affinity peptide-major histocompatibility complexes responses while inhibiting high-affinity ones. [Nat Immunol] Abstract | Press Release
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PUBLICATIONS (Ranked by impact factor of the journal)
Pleiotrophin Mediates Hematopoietic Regeneration via Activation of RAS
Scientists found that systemic administration of pleiotrophin (PTN), a protein that is secreted by BM-derived endothelial cells, substantially increased the survival of mice following radiation exposure and after myeloablative BM transplantation. In both models, PTN increased survival by accelerating the recovery of BM hematopoietic stem and progenitor cells in vivo. [J Clin Invest] Full Article

Hematopoietic RIPK1 Deficiency Results in Bone Marrow Failure Caused by Apoptosis and RIPK3-Mediated Necroptosis
To identify the lineages and cell types that depend on receptor-interacting serine/threonine-protein kinase 1 (RIPK1) for survival, scientists generated conditional Ripk1 mice. Tamoxifen administration to adult RosaCreERT2Ripk1fl/fl mice resulted in lethality caused by cell death in the intestinal and hematopoietic lineages. [Proc Natl Acad Sci USA] Abstract

Persistence of Virus Reservoirs in ART-Treated SHIV-Infected Rhesus Macaques after Autologous Hematopoietic Stem Cell Transplant
Researchers performed autologous hematopoietic stem cell transplantation (HSCT) in three Simian/Human Immunodeficiency Virus (SHIV)-infected, antiretroviral therapy (ART)-treated rhesus macaques using HSCs collected prior to infection and compared them to three SHIV-infected, ART-treated, untransplanted control animals to assess the effect of conditioning and autologous HSCT on viral persistence. [PLoS Pathog]
Full Article | Press Release

Single-Cell Analyses of Regulatory Network Perturbations Using Enhancer-Targeting TALEs Suggest Novel Roles for PU.1 during Hematopoietic Specification
Numerous transcription factors (TFs), including Scl and PU.1, are known regulators of developmental and adult hematopoiesis, but how they act within wider TF networks is still poorly understood. Researchers report transcription activator-like effectors (TALEs) engineered to target the PU.1-14kb and Scl+40kb transcriptional enhancers as efficient new tools to perturb the expression of these key hematopoietic TFs. [Development] Abstract | Full Article

Circadian and Circannual Variations in Cord Blood Hematopoietic Cell Composition
The authors observed that gestational age, birth weight and baby’s gender impacted concentrations of nucleated and hematopoietic progenitor cells in cord blood. They also show that uses of epidural anesthesia and of oxytocin were associated with higher concentrations of hematopoietic progenitor cells. [Haematologica]
Abstract | Full Article

Directed Differentiation of Embryonic Stem Cells Using a Bead-Based Combinatorial Screening Method
The authors describe three experiments comprising stepwise exposure of mouse or human embryonic cells to 10,000 combinations of serum-free differentiation media, through which they discovered multiple novel, efficient and robust protocols to generate a number of specific hematopoietic and neural lineages. [PLoS One]
Full Article | Press Release

Sall4 Overexpression Blocks Murine Hematopoiesis in a Dose-Dependent Manner
Scientists show that Sall4b is the predominant isoform in murine hematopoietic stem cells (HSCs) and progenitors. Overexpression of either Sall4a or Sall4b in HSCs or progenitors impairs hematopoietic colony formation and expansion in vitro. [Exp Hematol] Abstract


Delayed Hematopoietic Recovery after Auto-SCT in Patients Receiving Arsenic Trioxide-Based Therapy for Acute Promyelocytic Leukemia: A Multi-Center Analysis
Researchers retrospectively reviewed the clinical histories of 58 patients undergoing autologous hematopoietic SCT for acute promyelocytic leukemia at 21 institutions in the United States and Japan. Thirty-three of the patients received arsenic-based therapy prior to stem cell collection. [Bone Marrow Transplant] Abstract

A Phase I Study of the Safety, Pharmacokinetics, and Anti-Leukemic Activity of the Anti-CD123 Monoclonal Antibody, CSL360, in Relapsed, Refractory or High-Risk Acute Myeloid Leukemia (AML)
AML blasts express high levels of IL-3 receptor-α (CD123). CSL360 is a recombinant, chimeric IgG1, anti-CD123 monoclonal antibody that neutralizes IL-3 and demonstrates anti-leukemic activity in vitro. Investigators assessed safety, pharmacokinetics and bioactivity of weekly IV CSL360 for 12 weeks in 40 patients with advanced AML across five dose levels. [Leuk Lymphoma] Abstract

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Pleiotropic Roles of Notch Signaling in Normal, Malignant, and Developmental Hematopoiesis in the Human
The authors focus on recent developments in understanding the role of Notch signaling in the human hematopoietic system with an emphasis on hematopoietic initiation from human pluripotent stem cells and regulation within the bone marrow. [EMBO Rep] Abstract

Epigenetic Regulation of Hematopoietic Stem Cell Aging
The authors focus largely on the two most characterized epigenetic marks, DNA methylation and histone modifications, but also discuss the potential role of non-coding RNAs in regulating hematopoietic stem cell function during aging. [Exp Cell Res] Abstract

Visit our reviews page to see a complete list of reviews in the hematopoiesis research field.
ImmunoCellular Therapeutics Expands Cancer Immunotherapy Platform with Antigen-Specific T-Cell Technology Licensed from Caltech
ImmunoCellular Therapeutics, Ltd. announced that it has established a licensing agreement with the California Institute of Technology (Caltech) for exclusive rights to novel technology for the development of certain antigen specific T-cell immunotherapies for the treatment of cancer. The technology utilizes the patient’s own hematopoietic stem cells to create antigen-specific killer T-cells to treat cancer. [ImmunoCellular Therapeutics, Ltd.] Press Release

Celldex Therapeutics Initiates Pilot Study of CDX-301 in Allogeneic Hematopoietic Stem Cell Transplantation
Celldex Therapeutics, Inc. announced the initiation of a pilot study of CDX-301 for the mobilization and transplantation of allogeneic hematopoietic stem cells in patients with hematological malignancies undergoing hematopoietic stem cell transplantation. [Celldex Therapeutics, Inc.] Press Release

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NEW 4th Pan-European Conference on Hemoglobinopathies and Rare Anemias 2014
November 7-9, 2014
Athens, Greece

Visit our events page to see a complete list of events in the hematopoiesis community.
NEW Postdoctoral Position – Molecular Properties of Leukemic Stem Cells (BC Cancer Agency)

Postdoctoral Position – Cell Signaling in Hematopoietic Stem Cells (Cincinnati Children’s Hospital Medical Center)

Postdoctoral Position – Regenerative Effects of Some Mutations on Hematopoietic Stem Cells (Istanbul University Institute of Experimental Medicine)

Head of Cellular and Molecular Therapies Laboratory (NHS Blood & Transplant – Oxford)

Head of Cellular and Molecular Therapies Laboratory (NHS Blood & Transplant – Leeds)

Postdoctoral Fellow – Hematopoietic Stem Cells and Signaling Transduction (University of Pennsylvania)

Stem Cell Biology Program Director (Blood Research Institute of BloodCenter of Wisconsin)

Assistant or Associate Professor – Stem Cells and Regenerative Medicine (Baylor College of Medicine)

Research Associate – Cancer, Stem Cells, and Immunity Focusing on Membrane Proteins and Signaling Pathways (UT Southwestern Medical Center)

Postdoctoral Positions – Hematopoietic and Induced Pluripotent Stem Cells (Indiana University School of Medicine)

Scientist – Pluripotent Stem Cell Media Development, High Throughput Screening (STEMCELL Technologies Inc.)

Scientist – Cell Culture Support Products (STEMCELL Technologies Inc.)

Scientist – Immunology/Cell Separation (STEMCELL Technologies Inc.)

Research Associate – Cell Separation (STEMCELL Technologies Inc.)

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