Hematopoiesis News 8.38 September 26, 2017 | |
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TOP STORYUsing temporal–spatial resolved fate-mapping analysis and time-lapse imaging, investigators showed that the ventral endothelium in the zebrafish aorta–gonad–mesonephros and posterior blood island, the hematopoietic tissues previously known to generate HSCs and erythromyeloid progenitors, respectively, gives rise to a transient wave of T lymphopoiesis independent of HSCs. [J Exp Med] Abstract | |
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PUBLICATIONS(Ranked by impact factor of the journal)Researchers describe a complete workflow for the generation of humanized ossicles with an accessible bone-marrow (BM) microenvironment that faithfully recapitulates normal BM niche morphology and function. The humanized ossicles are formed by in situ differentiation of BM-derived mesenchymal stromal cells. Human hematopoietic cells can subsequently be transplanted directly into the ossicle marrow space or by intravenous injection. [Nat Protoc] Abstract Integrating Enhancer Mechanisms to Establish a Hierarchical Blood Development Program GATA-2-regulated enhancers increased Gata2 expression in hematopoietic stem/progenitor cells and control hematopoiesis. The +9.5-kb enhancer activated transcription in endothelium and HSCs, and its deletion abrogates HSC generation. The −77-kb enhancer activates transcription in myeloid progenitors, and its deletion impairs differentiation. [Cell Rep] Full Article | Graphical Abstract The authors demonstrated the following: (1) simplified HSC generation using transcription factor overexpression; (2) improved HSC output using c-Kit-deficient host mice, and (3) that teratomas can be transplanted and cryopreserved. [Stem Cell Reports] Full Article | Graphical Abstract Theaflavin Ameliorates Ionizing Radiation-Induced Hematopoietic Injury via the NRF2 Pathway Scientists explored the potential role of theaflavin (TF) in ionizing radiation-induced HSC injury and the underlying mechanism in a total body irradiation (TBI) mouse model. Their results showed that TF improved survival of irradiated wild-type mice and ameliorated TBI-induced hematopoietic injury by attenuating myelosuppression and myeloid skewing, increasing HSC frequency, and promoting reconstitution of irradiated HSCs. [Free Radic Biol Med] Abstract | Graphical Abstract Investigators used an unbiased in vivo chemical screen in a transgenic zebrafish embryo model and identified histone deacetylase inhibitors, particularly valproic acid, as significant enhancers of the number of phenotypic hematopoietic stem and progenitor cells (HSPCs), both in vivo and during ex vivo expansion. The long-term functionality of these expanded human HSPCs was verified in a xenotransplantation model with NSG mice. [Sci Rep] Full Article The authors examined the effect of the GNASR201C variant on HSC function. Ecoptic expression of GNASR201C supported transplantable HSC activity, and improved lymphoid output in secondary recipients. [Exp Hematol] Abstract Researchers elucidated the epigenetic effects of RNA in K562-microvesicles (MVs). Their findings revealed that increased miR-106a/b in K562-MVs accelerated the transformation process whereas decreased lincPOU3F3 delayed the transformation. [Oncol Rep] Abstract CLINICAL RESEARCHScientists present a single institution retrospective chart review of 15 hematopoietic stem cell transplant patients with veno-occlusive disease (VOD) treated with the combination of high-dose methylprednisolone and defibrotide. Their single center experience using both high-dose methylprednisolone and defibrotide showed a day +100 survival rate of 73% and an overall VOD complete resolution rate of 66.7%. [Biol Blood Marrow Transplant] Abstract Investigators applied the National Institutes of Health 2014 scoring criteria of chronic graft-versus-host-disease (cGvHD) to analyze a retrospective cohort of 362 allogeneic hematopoietic stem cell transplantation recipients focusing on cGvHD of liver. The overall incidence of liver cGvHD with a score of 3 by 1.5 years post-transplant was 5.8%. [PLoS One] Full Article | |
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REVIEWSEmerging Mechanisms of Long Noncoding RNA Function during Normal and Malignant Hematopoiesis Scientists review the current understanding of how lncRNAs help coordinate gene expression to modulate cell fate in the hematopoietic system. They focus on a growing number of mechanistic studies to synthesize emerging principles of lncRNA function, emphasizing how they facilitate diversification of gene programming during development. [Blood] Abstract Recent data suggested important roles for sphingosine 1-phosphate (S1P) signaling in engraftment, graft-versus-host disease (GvHD), graft-versus-leukemia (GvL) and other processes that occur during and after hemopoietic stem cell transplantation. Based on such data, pharmacological intervention via S1P modulation may have the potential to improve patient outcome by regulating GvHD and enhancing engraftment while permitting effective GvL. [Int J Mol Sci] Full Article The Slippery Slope of Hematopoietic Stem Cell Aging The finding that induced pluripotent stem cells were capable of fully regenerating multilineage hematopoiesis upon morula/blastocyst complementation provides compelling evidence that many aspects of HSC aging can be reversed, which proposes that a central mechanism underlying HSC aging is a failure to uphold the epigenomes associated with younger age. The authors discuss these findings in the context of the underlying causes that might influence on HSC aging, and the requirements and prospects for restoration of the aging HSC epigenome. [Exp Hematol] Abstract Visit our reviews page to see a complete list of reviews in the hematopoiesis research field. | |
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INDUSTRY NEWSResearchers Team Up to Find New Therapies for Childhood MDS, Leukemia Two researchers from the University of Wisconsin School of Medicine and Public Health will join forces to discover how a particular gene could affect a deadly, rare childhood genetic disease. [University of Wisconsin School of Medicine and Public Health] Press Release BioLineRx Ltd. announced the initiation of a Phase Ib/II trial for BL-8040 in combination with atezolizumab, an anti-PDL1 cancer immunotherapy from Genentech, a member of the Roche Group. The trial, known as the BATTLE study, will focus on the maintenance treatment of patients with intermediate- and high-risk acute myeloid leukemia (AML) who have achieved a complete response following induction and consolidation therapy. [BioLineRx Ltd.] Press Release Novartis announced that the European Commission approved Rydapt® for two indications in rare, hard-to-treat cancers. Rydapt is approved for use in combination with standard daunorubicin and cytarabine induction and high-dose cytarabine consolidation chemotherapy, and for patients in complete response followed by Rydapt single agent maintenance therapy, for adults with newly diagnosed AML who are FLT3 mutation-positive. [Novartis] Press Release | |
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POLICY NEWSWhat Germany’s Election Results Mean for Science As Germany reels from an unexpected surge for the far right in the elections, researchers don’t expect much effect on the country’s generous support for science. But with smaller parties standing to gain political influence, battles over issues such as the regulation of gene-edited organisms and how to cut greenhouse-gas emissions could grow fiercer. [Nature News] Editorial Publishers Go After Networking Site for Illicit Sharing of Journal Papers A major scientific publishing group is taking aim at a social networking site for allowing researchers to illegally post copies of their journal papers. The International Association of Scientific, Technical, and Medical Publishers in Oxford, U.K., and The Hague, the Netherlands, has written to ResearchGate, a networking website for researchers, to express concerns over its article-sharing practices. [ScienceInsider] Editorial United Kingdom Sees Dip in European Research Applications after Brexit Vote The number of researchers applying for Europe-funded Marie Curie fellowships in the United Kingdom has dipped slightly since the country’s vote to leave the European Union, data released to Nature show. But there is no evidence yet of a sharp collapse in interest, which some scientists had feared in the wake of the Brexit referendum. [Nature News] Editorial Canada Names New Chief Science Adviser Mona Nemer, a cardiology researcher and vice-president of research at the University of Ottawa, has been named Canada’s new Chief Science Adviser by Prime Minister Justin Trudeau. [ScienceInsider] Editorial
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EVENTSNEW 44th Annual Meeting of the European Society for Blood and Marrow Transplantation (EBMT) Visit our events page to see a complete list of events in the community.
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JOB OPPORTUNITIESNEW Postdoctoral Positions – Stem Cell and Cancer Biology (Johns Hopkins University) NEW Scientist – Hematopoietic Precursors and Immune Cells (Università di Genova) Postdoctoral Opportunities – Biology of Colorectal Cancer (Albert Einstein College of Medicine) Postdoctoral Fellow – Cancer Biology (UCSF Benioff Children’s Hospital) Postdoctoral Scholar – Hematopoiesis and Leukemia (Penn State College of Medicine) Director – Allogeneic Hematopoietic Stem Cell Transplantation (Princess Margaret Cancer Centre) Postdoctoral Fellow – Epigenetics and Immune Signaling in Cancer (Thomas Jefferson University) 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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