Hematopoiesis News Volume 11.02 | Jan 21 2020

TOP STORY

Control of Human Hemoglobin Switching by LIN28B-Mediated Regulation of BCL11A Translation

The authors showed that BCL11A is regulated at the level of messenger RNA (mRNA) translation during human hematopoietic development. Despite decreased BCL11A protein synthesis earlier in development, BCL11A mRNA continued to be associated with ribosomes. Through unbiased genomic and proteomic analyses, they demonstrated that the RNA-binding protein LIN28B, which was developmentally expressed in a pattern reciprocal to that of BCL11A, directly interacted with ribosomes and BCL11A mRNA. [Nat Genet] Abstract

(Ranked by impact factor of the journal)

A Wnt-Mediated Transformation of the Bone Marrow Stromal Cell Identity Orchestrates Skeletal Regeneration

Cell-lineage analysis using Cxcl12-creER mice revealed that quiescent Cxcl12-creER⁺ perisinusoidal bone marrow mesenchymal stem cells differentiated into cortical bone osteoblasts solely during regeneration. A combined single cell RNA-seq analysis demonstrated that these cells converted their identity into a skeletal stem cell-like state in response to injury, associated with upregulation of osteoblast-signature genes and activation of canonical Wnt signaling components along the single-cell trajectory. [Nat Commun] Full Article

Non-Invasive Characterization of Human Bone Marrow Stimulation and Reconstitution by Cell-Free Messenger RNA Sequencing

Using Next Generation Sequencing-based profiling, that cf-mRNA was enriched in transcripts derived from the bone marrow compared to circulating cells. Mechanistically, stimulation of specific bone marrow cell populations in vivo using growth factor pharmacotherapy showed that cf-mRNA reflected dynamic functional changes over time associated with cellular activity. [Nat Commun] Full Article

p53 Integrates Temporal WDR5 Inputs during Neuroectoderm and Mesoderm Differentiation of Mouse Embryonic Stem Cells

Wild-type Wdr5 or transient Wdr5 knockout promoted a distinct pattern of global chromatin accessibility and spurred neuroectodermal differentiation through an RbBP5-dependent process in which WDR5 binds to, and activated transcription of, neural genes. Wdr5 rescue after its prolonged inhibition targeted WDR5 to mesoderm lineage-specifying genes, stimulating differentiation toward mesoderm fates in a p53-dependent fashion. [Cell Rep] Abstract | Graphical Abstract

Multi-lineage Lung Regeneration by Stem Cell Transplantation across Major Genetic Barriers

Scientists demonstrated that durable tolerance toward mis-matched lung progenitors and their derivatives could be achieved without any chronic immune suppression, by virtue of co-transplantation with hematopoietic progenitors from the same donor. Initial proof of concept of this approach was attained by transplantation of fetal lung cells comprising both hematopoietic and non-hematopoietic progenitors. [Cell Rep] Full Article | Graphical Abstract

P53 and Parkin Co-Regulate Mitophagy in Bone Marrow Mesenchymal Stem Cells to Promote the Repair of Early Steroid-Induced Osteonecrosis of the Femoral Head

Investigators up-regulated Parkin and downregulated P53 in bone marrow mesenchymal stem cells (BMSCs). They found that this significantly enhanced mitophagy in BMSCs, decreased the accumulation of damaged mitochondria in cells, effectively resisted stress-induced BMSCs apoptosis and senescence, and improved the effect of BMSCs transplantation on early steroid-induced osteonecrosis of the femoral head. [Cell Death Dis] Full Article

Novel Mouse MicroRNA Chr13_novelMiR7354-5p Improves Bone Marrow-Derived Mesenchymal Stem Cell Differentiation into Insulin-Producing Cells

Researchers used next-generation sequencing to detect the miRNA expression profile of normal mouse pancreatic β-cells, non-β-cells, bone marrow mesenchymal stem cells and adipose-derived stem cells and determined relative miRNA expression levels in mouse pancreatic β-cells. [Mol Ther Nucleic Acids] Abstract | Full Article

Conditioned Medium From Human Tonsil-Derived Mesenchymal Stem Cells Enhances Bone Marrow Engraftment via Endothelial Cell Restoration by Pleiotrophin

Bone marrow cells (BMCs) isolated from C57BL/6 mice were transplanted via tail vein with or without tonsil-derived mesenchymal stem cell (T-MSCs) conditioned medium. Histological analysis of femurs showed increased bone marrow (BM) cellularity when T-MSC cardiomyocytes or recombinant human pleiotrophin, a cytokine readily secreted from T-MSCs with a function in hematopoiesis, was injected with BMCs. [Cells] Abstract | Download Full Article

CLINICAL RESEARCH

Protease-Activated Receptor Signaling Initiates α5β1-Integrin-Mediated Adhesion in Non-Haematopoietic Cells

Investigators report that the activation of protease-activated receptors PAR1 and PAR2 induced multiple signaling pathways to establish α5β1-integrin-mediated adhesion. PARs signaled via Gβγ and PI3K to α5β1-integrins to adopt a talin- and kindlin-dependent high-affinity conformation, which triggered fibronectin binding and initiated cell adhesion. [Nat Mater] Abstract

Low Incidence of Post-Transplant Lymphoproliferative Disorder after Allogeneic Stem Cell Transplantation in Patients with Lymphoma Treated with Rituximab

Japanese nationwide transplant registry data from 5270 patients with lymphoma after allogeneic hematopoietic stem cell transplantation (HSCT) were analyzed. Mature B-cell, T/NK-cell, and T-cell lymphoblastic subtypes accounted for 49%, 26%, and 9.6% of lymphoma cases, respectively. Rituximab was used in 1678 lymphoma patients, most of whom received HSCT for mature B-cell lymphoma. [Hematol Oncol] Abstract

Transplantation and Tracking of the Human Umbilical Cord Mesenchymal Stem Cell Labeled with Superparamagnetic Iron Oxide in Deaf Pigs

Researchers established a safe and effective approach to label the human umbilical cord MSCs derived from the Wharton’s Jelly with superparamagnetic iron oxide nanoparticles as a cell tracer. [Anat Rec] Abstract

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Unleashing the Cure: Overcoming Persistent Obstacles in the Translation and Expanded Use of Hematopoietic Stem Cell-Based Therapies

Investigators highlight the needs of the hematopoietic stem cell transplantation field (HSCT) and through examples from recent California Institute for Regenerative Medicine‐funded and other notable investigations, presents rationale for comprehensive, systematic, and focused strategies to unleash the full potential of HSCT, thereby enabling cures for a greatly expanded number of disorders and making HSCT feasible, accessible, and affordable to all who could benefit. [Stem Cells Transl Med] Full Article

Tendon Explant Models for Physiologically Relevant In Vitro Study of Tissue Biology – a Perspective

The authors overview of tissue explant models used in tendon research, with a specific focus on the value of explant culture systems for the controlled study of the tendon core tissue. They discuss their advantages, limitations and potential future utility. [Connect Tissue Res] Abstract

Visit our reviews page to see a complete list of reviews in the hematopoiesis research field.

Genmab Announces European Marketing Authorization for DARZALEX^® (Daratumumab) in Combination with Bortezomib, Thalidomide and Dexamethasone in Frontline Multiple Myeloma

Genmab A/S announced that the European Commission has granted marketing authorization for DARZALEX^® in combination with bortezomib, thalidomide and dexamethasone for the treatment of adult patients with newly diagnosed multiple myeloma who are eligible for autologous stem cell transplant. [Genmab A/S] Press Release

Janssen Seeks Expanded Use of IMBRUVICA^® (ibrutinib) in Combination with Rituximab for Patients with Previously Untreated Chronic Lymphocytic Leukaemia (CLL)

The Janssen Pharmaceutical Companies of Johnson & Johnson today announced the submission of a Type II variation application to the European Medicines Agency seeking to expand the label of IMBRUVICA^® to include ibrutinib in combination with rituximab for the first-line treatment of patients with chronic lymphocytic leukaemia. [The Janssen Pharmaceutical Companies (Business Wire, Inc.)] Press Release

University of Delaware’s Emily Day Among Researchers Funded Through Science Center Program

Assistant professor Emily Day is developing nanoparticle carrier systems to deliver therapeutic treatment directly to stem cells without the need to remove them from the body. Now, with $200,000 in new funding through a QED grant from the University City Science Center in Philadelphia, Day will test whether methods developed in the lab are effective and can be commercialized. [University of Delaware] Press Release

Campus Attacks by Nationalists and Police Alarm India’s Scientific Community

The attack on one of India’s most prestigious universities sent shock waves around the country and is the latest sign that the political forces tearing apart Indian society are also affecting the country’s academic community. Students at JNU, a liberal bastion, had been on strike for months against both a major hike in student fees and the government’s controversial Citizenship Amendment Act, widely decried as discriminatory against Muslims. [ScienceInsider] Editorial

Moffitt Cancer Center Details Links of Fired Scientists to Chinese Talent Programs

Six Florida cancer researchers who were dismissed last month for hiding their ties to a Chinese medical university appear to have been motivated by simple greed and a disregard for both institutional and federal rules. [ScienceInsider] Editorial

NEW 27^th International Molecular Medicine Tri-Conference
March 1-4, 2020
San Francisco, California, United States

Visit our events page to see a complete list of events in the community.

NEW Postdoctoral Fellowship – Personalized Cancer Treatments (MGH Cancer Center)

Scientist – Hematopoietic Stem and Progenitor Cell Biology (STEMCELL Technologies Inc.)

Team Leader- Clonal Evolution in Leukemia (Institute of Cancer Research)

Team Leader – Clonal Evolution in Leukemia (Institute of Cancer Research)

Faculty Position – Cancer Epidemiology (MD Anderson Cancer Center)

Research Fellow – Hematology & Blood Disorders (New York Blood Center)

Postdoctoral Fellow – Erythropoiesis (Mount Sinai School of Medicine)

Assistant/Associate Professor – Hematology & Oncology (UC Davis School of Medicine)

Associate/Professor – Hematology & Oncology (UC Davis School of Medicine)

Postdoctoral Fellowship – Leukemia Pathogenesis (BC Cancer)

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