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JCI online ahead of print table of contents for April 24, 2014
Date:4/24/2014

Ex vivo expansion of hematopoietic stem cells from cord blood

Compared to hematopoietic stem cells (HSCs) isolated from adults, HSCs isolated from cord blood (CB) have enhanced proliferative potential and can lead to hematological reconstitution when engrafted in children with hematological malignancies or genetic defects. Unfortunately, small numbers of HSCs are present in single CB collections, limiting their use as grafts for adults. For several decades investigators have used a variety of strategies to expand the numbers of CB HSC ex vivo with limited success. Evidence indicates that accumulation of epigenetic modifications influences preservation of stem cell characteristics in HSC daughter cells; therefore, in this issue of the Journal of Clinical Investigation, Pratima Chaurasia and colleagues at Mount Sinai School of Medicine expanded CB HSCs in the presence of histone deacetylase inhibitors (HDACIs) and evaluated their characteristics. Valproic acid (VPA)-treated CB HSCs produced greater numbers of HSCs that expressed several pluripotency genes. Compared to conventionally expanded CB HSCs, VPA-treated HSCs were more efficient in repopulating the bone marrow and establishing hematopoietic populations in immune deficient mice. In an accompanying Commentary, Hal Broxmeyer of the Indiana University School of Medicine discusses how these findings enhance our understanding of HSC function and could provide clinical benefit.

TITLE: Epigenetic reprogramming induces the expansion of cord blood stem cells

AUTHOR CONTACT: Ronald Hoffman
Mount Sinai School of Medicine, New York, NY, USA
Phone: 212-241-1948; Fax: 212-876-5276; E-mail: ronald.hoffman@mssm.edu

OR

Pratima Chaurasia
Mount Sinai School of Medicine, New York, NY, USA
Phone: 212.241.1766; Fax: 212.876.5276; E-mail: pratima.chaurasia@mssm.edu

View this article at: http://www.jci.org/articles/view/70313

ACCOMPANYING COMMENTARY

TITLE: Inhibiting HDAC for human hematopoietic stem cell expansion

AUTHOR CONTACT: Hal E. Broxmeyer
Indiana University School of Medicine, Indianapolis, IN, USA
Phone: 317-274-7504 (Tel); Fax: 317-274-7592; E-mail: hbroxmey@iupui.edu

View this article at: http://www.jci.org/articles/view/75803


Receptors in the brain mediate the weight loss effects of GLP1 agonists

Glucagon-like peptide-1 (GLP1) analogs are able to achieve both weight loss and glucose tolerance, both of which are crucial for controlling type 2 diabetes (T2D). GLP1 receptors (GLP1Rs) are present in the brain, but it is not clear if the brain does indeed mediate the weight loss and glucose lowering effects of GLP1 analogs. In this issue of the Journal of Clinical Investigation, Stephanie Sisley and colleagues at Cincinnati Children's Hospital Medical Center evaluated the effects of the GLP1 agonist liraglutide in animals lacking GLP1R in the central nervous system (CNS) or in visceral nerves and found that liraglutide had no effect on weight loss or food intake in these animals, even those fed a high fat diet. Interestingly, liragludtie administration did lower glucose levels in animals lacking GLP1R in either the CNS or visceral nerves. Together, these data indicate that neuronal GLP1Rs mediate weight loss and anorectic effects, but do not mediate glucose lowering.

TITLE: Neuronal GLP1R mediates liraglutide's anorectic but not glucose-lowering effect

AUTHOR CONTACT: Stephanie Sisley
Baylor College of Medicine, Houston, TX, USA
Phone: 513-465-8701; Fax: 713-798-7057; E-mail: steph.sisley@yahoo.com

View this article at: http://www.jci.org/articles/view/72434


CARDIOLOGY

TITLE: Epac1dependent phospholamban phosphorylation mediates the cardiac response to stresses

AUTHOR CONTACT: Satoshi Okumura
Tsurumi University, Yokohama, UNK, JPN
Phone: 011-81-45-580-8476; Fax: 011-81-45-585-2889; E-mail: okumura-s@tsurumi-u.ac.jp

View this article at: http://www.jci.org/articles/view/64784

ONCOLOGY

TITLE: Mesenchymal gene program-expressing ovarian cancer spheroids exhibit enhanced mesothelial clearance

AUTHOR CONTACT: Joan Brugge
Harvard Medical School, Boston, MA, USA
Phone: 617/432-3974; Fax: 617-432-3969; E-mail: Joan_Brugge@hms.harvard.edu

View this article at: http://www.jci.org/articles/view/69815

TITLE: The tumor suppressor folliculin regulates AMPK-dependent metabolic transformation

AUTHOR CONTACT: Arnim Pause
McGill University, Montreal, PQ, CAN
Phone: 514-398-1521; E-mail: arnim.pause@mcgill.ca

View this article at: http://www.jci.org/articles/view/71749

TITLE: ZEB1 sensitizes lung adenocarcinoma to metastasis suppression by PI3K antagonism

AUTHOR CONTACT: Jonathan Kurie
University of Texas MD Anderson Cancer Center, Houston, TX, USA
Phone: 713-745-6747; Fax: 713-792-1220; E-mail: jkurie@mdanderson.org

OR

Yanan Yang
Mayo Clinic, Rochester, MN, USA
Phone: 507.284.8754; Fax: 507.284.9207; E-mail: yang.yanan@mayo.edu.

View this article at: http://www.jci.org/articles/view/72171

IMMUNOLOGY

TITLE: Intrinsic TGF-β signaling promotes age-dependent CD8+ T cell polyfunctionality attrition

AUTHOR CONTACT: Imitaz Khan
George Washington University, Washington, DC, USA
Phone: 202.994.2863; Fax: 202.994.2913; E-mail: imti56@gwu.edu

View this article at: http://www.jci.org/articles/view/70522

NEUROSCIENCE

TITLE: Peripheral nervous system plasmalogens regulate Schwann cell differentiation and myelination

AUTHOR CONTACT: Pedro Brites
Instituto de Biologia Molecular e Celular, Porto, , PRT
Phone: 00351226074900; Fax: ; E-mail: pedro.brites@ibmc.up.pt

View this article at: http://www.jci.org/articles/view/72063

ENDOCRINOLOGY

TITLE: Estrogen promotes Leydig cell engulfment by macrophages in male infertility

AUTHOR CONTACT: Xiangdong Li
State Key Laboratory of Agro-Biotechnology, Beijing, CHN
Phone: 86-1062734389; E-mail: xiangdongli@cau.edu.cn

View this article at: http://www.jci.org/articles/view/59901


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Contact: Corinne Williams
press_releases@the-jci.org
Journal of Clinical Investigation
Source:Eurekalert

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