Hematopoiesis News Volume 5.06 | Feb 18 2014

Stage-Specific Control of Early B Cell Development by the Transcription Factor Ikaros
The transcription factor Ikaros is an essential regulator of lymphopoiesis. Scientists studied its B cell-specific function by conditional inactivation of the gene encoding Ikaros in pro-B cells. B cell development was arrested at an aberrant ‘pro-B cell’ stage characterized by increased cell adhesion and loss of signaling via the pre-B cell signaling complex. [Nat Immunol] Abstract | Press Release

Expandable Megakaryocyte Cell Lines Enable Clinically Applicable Generation of Platelets from Human Induced Pluripotent Stem Cells
Researchers developed a clinically applicable strategy for the derivation of functional platelets from human pluripotent stem cells (PSCs). This approach involves the establishment of stable immortalized megakaryocyte progenitor cell lines from PSC-derived hematopoietic progenitors through the overexpression of BMI1 and BCL-XL to respectively suppress senescence and apoptosis and the constrained overexpression of c-MYC to promote proliferation. [Cell Stem Cell] Abstract | Graphical Abstract | Press Release

T Cell Repertoire following Autologous Stem Cell Transplantation for Multiple Sclerosis
In a Phase II study of hematopoietic stem cell transplantation (HSCT) for poor-prognosis multiple sclerosis, the authors used high-throughput deep TCRβ chain sequencing to assess millions of individual TCRs per patient sample. They found that HSCT has distinctive effects on CD4⁺ and CD8⁺ T cell repertoires. [J Clin Invest]
Full Article | Press Release

G-CSF Regulates Hematopoietic Stem Cell Activity, in Part, through Activation of Toll-Like Receptor Signaling
Scientists showed that treatment with granulocyte-colony stimulating factor (G-CSF) induces expansion and increased quiescence of phenotypic hematopoietic stem cells (HSCs), but causes a marked, cell-autonomous HSC repopulating defect associated with induction of toll-like receptor expression and signaling. [Leukemia] Abstract

Essential Role of BRG, the ATPase Subunit of BAF Chromatin Remodeling Complexes, in Leukemia Maintenance
The authors showed using quantitative proteomics that BAF complexes expressed in leukemia are specifically assembled around the BRG ATPase. Using a mouse model of acute myeloid leukemia, they demonstrate that BRG is essential for leukemia maintenance, as leukemic cells lacking BRG rapidly undergo cell-cycle arrest and apoptosis. [Blood] Abstract | Press Release

Functional Assessment of Hematopoietic Niche Cells Derived from Human Embryonic Stem Cells
To evaluate hematopoietic niche cell populations isolated from human embryonic stem cells (hESCs), scientists tested the ability of hESC-derived stromal lines to support CD34+ umbilical cord blood and hESC-derived CD34+45+ cells in long-term culture initiating cell assays. [Stem Cells Dev] Abstract

FGF-23 Is a Negative Regulator of Prenatal and Postnatal Erythropoiesis
Researchers report that loss of Fibroblast Growth Factor-23 (FGF-23) results in increased hematopoietic stem cell frequency associated with increased erythropoiesis in peripheral blood and bone marrow in young adult mice. [J Biol Chem] Abstract

Quality of Functional Hematopoietic Stem/Progenitor Cells from Cryopreserved Human Umbilical Cord Blood
Researchers examined the quality of umbilical cord blood (UCB) cryopreserved for 2, 4 and 6 years. The following parameters and procedures were used to test individual units of cryopreserved UCB: the number of total nucleated cells, cell viability, CFU-GM assay, T-cell activation in vitro and hematopoietic stem cell engraftment in NOD/SCID mice in vivo. [Vox Sang] Abstract

CLINICAL RESEARCH

Myeloablative I-131-Tositumomab with Escalating Doses of Fludarabine and Autologous Hematopoietic Transplantation for Adults Aged ≥ 60 Years with B-Cell Lymphoma
Myeloablative therapy and autologous stem cell transplant is underutilized in older patients with B-cell non-Hodgkin lymphoma. Investigators hypothesized that myeloablative doses of ¹³¹I-tositumomab could be augmented by concurrent fludarabine based on preclinical data indicating synergy. [Biol Blood Marrow Transplant] Abstract

Very Early Onset Inflammatory Bowel Disease Associated with Aberrant Trafficking of IL-10R1 and Cure by T Cell Replete Haploidentical Bone Marrow Transplantation
Researchers investigated the molecular pathomechanism of a novel intronic IL10RA mutation and describe a new therapeutic approach of T cell replete haploidentical hematopoietic stem cell transplantation. [J Clin Immunol] Abstract

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Cytolon AG Global Cord Program Partners with Mediware for Stem Cell, Cord Blood Bank Solution
Mediware Information Systems, Inc. and Cytolon AG agreed to collaborate on improving IT tools for banking and matching of hematopoietic stem cells derived from umbilical cord blood donations. [Mediware Information Systems, Inc.] Press Release

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NEW Research Technologist – Pluripotent Stem Cells (STEMCELL Technologies Inc.)

NEW Research Technologist – Particle Chemistry (STEMCELL Technologies Inc.)

NEW Research Technologist – PSC Biology and Bioengineering (STEMCELL Technologies Inc.)

Postdoctoral Fellow – Erythropoiesis and Iron Metabolism (University of Wisconsin – Madison)

Postdoctoral Position – Hematopoietic Stem Cell Biology (St. Jude Children’s Research Hospital)

Postdoctoral Positions – New Models of Hematopoiesis and Hematopoietic Disorders (Mount Sinai Medical Center)

Assistant Professorship – Hematopoietic Stem Cells and Microenvironment (University of Zurich)

Postdoctoral Fellow – Hematopoietic Stem Cell and Leukemia Research (City of Hope)

Postdoctoral Position – Hematopoietic Stem Cell Physiology and Bone Marrow Failure (University of Michigan)

Research Associate – Normal & Leukemic Stem Cells (King’s College London)

Postdoctoral Fellow – Morphogenetic Signaling Pathways in Development and Disease (University of Rochester Medical Center)

Scientific Affairs Coordinator (American Society of Hematology)

Postdoctoral Position – Erythroid and Myeloid Differentiation of Hematopoietic Stem Cells (Imagine Institute)

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