Mesenchymal Cell News Volume 10.46 | Nov 20 2018

TOP STORY

Mettl3-Mediated m⁶A RNA Methylation Regulates the Fate of Bone Marrow Mesenchymal Stem Cells and Osteoporosis

Researchers showed that conditional knockout of the N⁶-methyladenosine (m⁶A) methyltransferase Mettl3 in bone marrow MSCs induced pathological features of osteoporosis in mice. Mettl3 loss-of-function resulted in impaired bone formation, incompetent osteogenic differentiation potential and increased marrow adiposity. [Nat Commun] Full Article

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IN VITRO

H3K36 Trimethylation Mediated by SETD2 Regulates the Fate of Bone Marrow Mesenchymal Stem Cells

Scientists identified a SET-domain-containing 2 (SETD2) functional target gene, lipopolysaccharide-binding protein (LBP), on which H3 lysine 36 trimethylation (H3K36me3) was enriched, and its expression was affected by Setd2 deficiency. Overexpression of LBP could partially rescue the lack of osteogenesis and enhanced adipogenesis resulting from the absence of Setd2 in bone marrow-derived MSCs. [PLoS Biol] Full Article

A Reciprocal Role of the Smad4-Taz Axis in Osteogenesis and Adipogenesis of Mesenchymal Stem Cells

The authors demonstrated a Smad4-Taz axis as a new intrinsic regulator for adipo-osteogenic differentiation of MSCs and showed that this function of Smad4 was independent of the TGF-β signal. [Stem Cells] Abstract | Full Article

Calcium Supplementation Enhanced Adipogenesis and Improved Glucose Homeostasis through Activation of Camkii and PI3K/Akt Signaling Pathway in Porcine Bone Marrow Mesenchymal Stem Cells (pBMSCs) and Mice Fed High Fat Diet (HFD)

Extracellular calcium ([Ca²⁺]_o) stimulated pBMSCs adipogenesis by increasing intracellular [Ca²⁺] levels and activating the Ca²⁺/calmodulin-dependent protein kinase II (CaMKII) and PI3K/Akt-FoxO1 pathways. In addition, [Ca²⁺]]_o) promoted glucose uptake/utilization by enhancing AS160 phosphorylation, glucose transporter 4 expression and translocation. [Cell Physiol Biochem] Full Article

HDAC8, a Potential Therapeutic Target, Regulates Proliferation and Differentiation of Bone Marrow Stromal Cells in Fibrous Dysplasia

Compared with normal bone marrow MSCs (BMSCs), fibrous dysplasia (FD) BMSCs exhibited significantly high proliferation and weak osteogenic capacity in response to histone deacetylase 8 (HDAC8) upregulation and tumor protein 53 (TP53) downregulation. Moreover, inhibition of cAMP reduced HDAC8 expression, increased TP53 expression and resulted in the improvement of the FD phenotype. [Stem Cells Transl Med] Full Article

Zika Virus Infection Perturbs Osteoblast Function

Researchers studied the effect of Zika virus (ZIKV) infection on osteoblast differentiation, maturation and function by quantifying activity and gene expression of key biomarkers, using human bone marrow-derived MSCs. MSCs were induced to differentiate into osteoblasts and they found that osteoblasts were highly susceptible to ZIKV infection. [Sci Rep] Full Article

AP2a Enhanced the Osteogenic Differentiation of Mesenchymal Stem Cells by Inhibiting the Formation of YAP/RUNX2 Complex and BARX1 Transcription

Investigators showed that AP2a could compete with RUNX2, a key transcription factor in osteogenic differentiation, to recruit YAP and release the inhibition of RUNX2 activity from YAP by forming YAP-AP2a protein complex. YAP-AP2a protein complex also interacted with the BARX1 promoter through AP2a, inhibiting the transcription of BARX1. [Cell Prolif] Full Article

IN VIVO

Runx2 Regulates Cranial Suture Closure by Inducing Hedgehog, Fgf, Wnt, and Pthlh Signaling Pathway Gene Expression in Suture Mesenchymal Cells

The closure of posterior frontal and sagittal sutures was completely interrupted in Runx2^+/– mice, and the proliferation of suture mesenchymal cells and their condensation were less than those in wild-type mice. [Hum Mol Genet] Abstract

Epigenetically Modified Cardiac Mesenchymal Stromal Cells Limit Myocardial Fibrosis and Promote Functional Recovery in a Model of Chronic Ischemic Cardiomyopathy

Human cardiac mesenchymal cells pre-treated with entinostat or DMSO diluent control were delivered intramyocardially in an athymic nude rat model of chronic ischemic cardiomyopathy 30 days after a reperfused myocardial infarction. Indices of cardiac function were assessed by echocardiography and left ventricular Millar conductance catheterization 35 days after treatment. [Basic Res Cardiol] Abstract

Tumor-Targeted Immunotherapy by Using Primary Adipose-Derived Stem Cells and an Antigen-Specific Protein Vaccine

Either subcutaneously co-inoculated with cancer cells or systemically administered after tumor growth, adipose-derived stem cells labeled with enhanced green fluorescent protein and combined with modified E7’ antigen cells showed significant antitumor activity when combined with the protein vaccine in both colon and lung cancer in mice. [Cancers] Full Article

Mesenchymal Stem Cell Administration Attenuates Colon Cancer Progression by Modulating the Immune Component within the Colorectal Tumor Microenvironment

Treatment with bone marrow-derived MSCs significantly reduced both cancer initiation and cancer progression by increasing the number of tumor-free animals as well as decreasing the number and the size of the tumors by half, thereby extending their lifespan. The attenuation of cancer progression was mediated by the capacity of the MSCs to modulate the immune component. [Stem Cells Transl Med] Full Article

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Autogenic Mesenchymal Stem Cells for Intervertebral Disc Regeneration

A systematic review of the literature is conducted to clarify the outcomes of autologous MSC injections for the regeneration of the intervertebral disc. The authors prove MSC injection to be a safe and feasible option for intervertebral disc regeneration in early-degeneration stage patients. [Int Orthop] Abstract

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DFG to Fund 15 New Research Training Groups

The Deutsche Forschungsgemeinschaft (DFG) is establishing 15 new Research Training Groups (RTGs) to further support early career researchers. This was decided by the responsible Grants Committee during its autumn session in Bonn. The new RTGs will receive a total of approximately €71 million for an initial period of four and a half years, starting from April 2019. [DFG] Press Release

EMBO Welcomes Twenty-Six New Young Investigators

EMBO has selected 26 life science researchers within their first four years as group leaders to become EMBO Young Investigators. They join an active network of 102 current and 314 past Young Investigators and will receive support from EMBO during the foundation of their first independent laboratory. [EMBO] Press Release

BrainStorm Cell Therapeutics Announces Submission of IND for NurOwn^® in Progressive Multiple Sclerosis

BrainStorm Cell Therapeutics Inc. announced that it has submitted an Investigational New Drug (IND) application with the FDA to initiate a Phase II study of NurOwn^® in patients with progressive multiple sclerosis. [BrainStorm Cell Therapeutics Inc.] Press Release

French Science Behemoth Launches Research-Integrity Office

France’s national research centre, the CNRS, has announced plans to create its first office of research integrity to investigate scientific misconduct and promote good research practice. [Nature News] Editorial

In Reversal, NSF Lifts Proposal Limits on Biologists

In a reversal, the National Science Foundation (NSF) will no longer restrict researchers to only one proposal submission per year to the biology directorate’s three core tracks in which they are listed as a principal investigator (PI) or co-PI. [ScienceInsider] Editorial

NEW Keystone Symposia: Genome Engineering: From Mechanisms to Therapies
February 19-23, 2019
Victoria, British Columbia, Canada

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NEW Postdoctoral Position – Regenerative Medicine, Stem Cells & Bioengineering (Igenomix Foundation)

Postdoctoral Research Fellow – Biomaterials Engineering (Karolinska Institute)

Associate Professor/Professor – Regenerative Medicine or Stem Cell Biology (University of Toronto)

Postdoctoral Researcher – Tissue Engineering & Organs on a Chip (OHSU School of Dentistry)

Professor – Stem Cell & Regenerative Medicine (University College London)

Assistant/Associate Professors – Center for Stem Cell & Organoid Medicine (Cincinnati Children’s Hospital Medical Center)

Faculty Position – Department of Biochemistry & Molecular Biology (Mayo Clinic)

Postdoctoral Fellowships – Nanomedicine & Biomedical Engineering (University of British Columbia)

PhD Positions/ Early Stage Researcher Positions – EU Horizon 2020 MSCA-ITN Project (Renal Tool Box)

Assistant Professor – Department of Stem Cell and Regenerative Biology (Harvard University)

Tenure Track Group Leader Position – Mechanisms in Multicellularity or Tissue Regulation (Friedrich Miescher Institute for Biomedical Research)

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