Hematopoiesis News 9.12 March 27, 2018 | |
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TOP STORYStem Cell Niche-Specific Ebf3 Maintains the Bone Marrow Cavity Using lineage tracing, researchers found that the transcription factor early B-cell factor 3 (Ebf3) is preferentially expressed in CXC chemokine ligand 12-abundant reticular (CAR)/leptin receptor-positive (LepR+) cells and that Ebf3-expressing cells are self-renewing mesenchymal stem cells in adult marrow. When Ebf3 was deleted in CAR/LepR+ cells, HSC niche function was severely impaired, and bone marrow was osteosclerotic with increased bone in aged mice. [Genes Dev] Abstract | |
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PUBLICATIONS(Ranked by impact factor of the journal)Scientists identified familial and early-onset multiple myeloma kindreds with truncating mutations in LSD1/KDM1A, an epigenetic transcriptional repressor that primarily demethylates histone H3 on lysine 4 and regulates hematopoietic stem cell self-renewal. [Cancer Res] Abstract BET-Inhibition by JQ1 Promotes Proliferation and Self-Renewal Capacity of Hematopoietic Stem Cells JQ1 induced proliferation of long term-hematopoietic stem cells, thereby increasing stem cell numbers. Due to increased numbers, JQ1-treated hematopoietic stem cells engrafted better after stem cell transplantation and repopulated the hematopoietic system significantly faster after sublethal myeloablation. [Haematologica] Abstract | Full Article Using a transgenic mouse expressing JAK2V617F specifically in all hematopoietic cells (including hematopoietic stem/progenitor cells) and endothelial cells, investigators showed that the JAK2V617F-mutant hematopoietic stem/progenitor cells are relatively protected by the JAK2V617F-bearing vascular niche from an otherwise lethal dose of irradiation during conditioning for stem cell transplantation. [Haematologica] Abstract | Full Article A Humanized Mouse Model Generated Using Surplus Neonatal Tissue The authors describe the NeoThy humanized mouse model created using non-fetal human tissue sources, cryopreserved neonatal thymus and umbilical cord blood HSCs. The NeoThy has equivalent frequencies of engrafted human immune cells compared with fetal tissue humanized mice and exhibits T cell function in assays of ex vivo cell proliferation, interferon γ secretion, and in vivo graft infiltration. [Stem Cell Reports] Full Article Researchers devised three experimental approaches that enable them to monitor quiescent and proliferating HSCs and provided the direct evidence that the mitochondrial unfolded protein response is activated upon HSC transition from quiescence to proliferation, and more broadly, mitochondrial integrity is actively monitored at the restriction point to ensure metabolic fitness before stem cells are committed to proliferation. [Aging Cell] Full Article Notch and AHR Signaling Impact Definitive Hematopoiesis from Human Pluripotent Stem Cells Scientists developed a chemically defined, serum and feeder‐free directed differentiation platform to generate hematopoietic stem‐progenitor cells and resultant adult‐type progeny from induced pluripotent stem cells. They demonstrated the stage‐specific roles of two key signaling pathways, Notch and the Aryl hydrocarbon receptor, in the derivation of definitive hematopoietic cells. [Stem Cells] Abstract Engineering a Multicellular Vascular Niche to Model Hematopoietic Cell Trafficking Researchers developed an engineered human vascular marrow niche to examine the three-dimensional cell interactions that direct hematopoietic cell trafficking. [Stem Cell Res Ther] Full Article Scientists showed that conditional deletion of Tmem30a, the beta subunit of P4-ATPase flippase complex, caused pancytopenia in mice. Tmem30a deficiency resulted in depletion of lineage-committed blood cells in the peripheral blood, spleen, and bone marrow. [Am J Pathol] Abstract SWI/SNF Subunit Expression Heterogeneity in Human Aplastic Anemia Stem/Progenitors Gene expression analysis identified a significant loss of SWI/SNF core component SMARCC1 along with ARID1B, ACTL6A and SMARCD1 in human aplastic anemia bone marrow CD34+ HSC and progenitors (HSPCs) compared to normal HSPCs. [Exp Hematol] Abstract | Graphical Abstract Mechanistic studies demonstrated that human cytomegalovirus (HCMV) promotes the differentiation of hematopoietic progenitor cells into a monocyte subset by activating cellular signal transducer and activator of transcription 3. In turn, this monocyte subset generated a high level of nitric oxide to silence HCMV immediate-early transcription and promote viral latency. [Nat Microbiol] Abstract CLINICAL RESEARCHThe pivotal Phase II PACE trial evaluated efficacy and safety of ponatinib at a starting dose of 45 mg once daily in 449 patients with chronic myeloid leukemia or Philadelphia chromosome–positive acute lymphoblastic leukemia resistant/intolerant to dasatinib or nilotinib, or with BCR ABL1T315I. [Blood] Abstract | Press Release | |
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REVIEWSScientists summarize recent discoveries of mesenchymal stromal cells as part of the hematopoietic niche and as myofibroblast precursors and discuss potential therapeutic strategies in the specific targeting of fibrotic transformation in bone marrow fibrosis. [J Pathol] Abstract Current Approaches in Biomaterial-Based Hematopoietic Stem Cell Niches The factors that regulate the HSCs in vivo are explained and their applications in the engineering of a bone marrow biomaterial-based platform are discussed. In addition, current approaches, challenges, and the future direction of a biomaterial-based culture and expansion of the HSC are examined. [Acta Biomater] Abstract | Graphical Abstract The authors provide a summary of data from animal and human studies describing the relationship between marrow adipose tissue and hematopoiesis, bone mineral density, bone strength, and metabolic function. [Bone] Abstract Visit our reviews page to see a complete list of reviews in the hematopoiesis research field. | |
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INDUSTRY NEWSHelix BioPharma Corp. announced the completion of the collaboration agreement with ProMab Biotechnologies, Inc. to develop novel antibody and chimeric antigen receptor T-cell therapy for particular hematological malignancies. [Helix BioPharma Corp. (GlobeNewswire, Inc.)] Press Release AbbVie and the International Myeloma Foundation announced they have entered into a collaboration to conduct a landmark retrospective chart review study to better understand and help manage multiple myeloma, the second most common blood cancer. [AbbVie] Press Release The Multiple Myeloma Research Foundation announced that, as part of its $15M Immunotherapy Initiative, it has awarded $7M in funding to three ground-breaking research programs led by renowned myeloma researchers. [Multiple Myeloma Research Foundation] Press Release Novartis Drug Tasigna® Approved by FDA to Treat Children with Rare Form of Leukemia Novartis announced that the FDA expanded the indication for Tasigna® to include treatment of first- and second-line pediatric patients one year of age or older with Philadelphia chromosome-positive chronic myeloid leukemia in the chronic phase. [Novartis] Press Release | |
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POLICY NEWSCambridge Analytica Controversy Must Spur Researchers to Update Data Ethics Revelations keep emerging in the Cambridge Analytica personal-data scandal, which has captured global public attention. But when the dust settles, researchers harvesting data online will face greater scrutiny. And so they should. [Nature News] Editorial Duke’s Mishandling of Misconduct Prompts New U.S. Government Grant Oversight The U.S. National Institutes of Health imposed unusual new requirements on researchers based at Duke University in Durham, North Carolina, who receive federal funds. The changes are a response to concerns over how the institution handled recent cases involving research misconduct and grant management. [ScienceInsider] Editorial Massive Cyberhack by Iran Allegedly Stole Research from 320 Universities, Governments, and Companies Nine Iranians working on behalf of the Islamic Revolutionary Guard Corps hacked the computers of 7998 professors at 320 universities around the world over the past five years, an indictment filed by a federal grand jury alleges. [ScienceInsider] Editorial
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EVENTSNEW 37th World Congress of Hematology (ISH) Visit our events page to see a complete list of events in the community.
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JOB OPPORTUNITIESNEW Tenure Track Faculty Position – Hematopathology (University of Virginia) Postdoctoral Scholar – Clonal Hematopoiesis (Stanford University) Postdoctoral Fellow – Hematopoiesis and Hematopoietic Stem Cell Biology (City of Hope) Postdoctoral Position – Tregs in the Hematopoietic Stem Cell Niche (Columbia University) Postdoctoral Associate – Stem Cell Biology and Cancer Epigenetics (The Jackson Laboratory) Postdoctoral Fellow – Stem Cells, Development & Cancer (Albert Einstein College of Medicine) Postdoctoral Research Fellow – Hematopoiesis (Fred Hutchinson Cancer Research Center) Postdoctoral Positions – Hematopoietic Stem Cells (Memorial Sloan Kettering Cancer Center) Postdoctoral Associate – Stem Cell Biology (Duke University) Postdoctoral Fellowship – Functional Genomics of Human Hematopoiesis (Harvard Medical School) Postdoctoral Positions – Translational Leukemia (NYU Langone School of Medicine) Postdoctoral Research Associate – Mechanisms of Leukemia (University of Virginia) Postdoctoral Position – Hematology and Cancer Biology (University of Florida) Recruit Top Talent: Reach potential candidates by posting your organization’s career opportunities on the Connexon Creative Job Board at no cost.
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