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https://www.readbyqxmd.com/read/28092268/phenotypic-outcomes-in-mouse-and-human-foxc1-dependent-dandy-walker-cerebellar-malformation-suggest-shared-mechanisms
#1
Parthiv Haldipur, Derek Dang, Kimberly A Aldinger, Olivia K Janson, Fabien Guimiot, Homa Adle-Biasette, William B Dobyns, Joseph R Siebert, Rosa Russo, Kathleen J Millen
FOXC1 loss contributes to Dandy-Walker malformation (DWM), a common human cerebellar malformation.  Previously we found that complete Foxc1 loss leads to aberrations in proliferation, neuronal differentiation and migration in the embryonic mouse cerebellum (Haldipur et al., 2014). We now demonstrate that hypomorphic Foxc1 mutant mice have granule and Purkinje cell abnormalities causing subsequent disruptions in postnatal cerebellar foliation and lamination. Particularly striking is the presence of a partially formed posterior lobule echoing the posterior vermis DW "tail sign" observed in human imaging studies...
January 16, 2017: ELife
https://www.readbyqxmd.com/read/28092084/iron-availability-compromises-not-only-oligodendrocytes-but-also-astrocytes-and-microglial-cells
#2
Maria Victoria Rosato-Siri, Leandro Marziali, María Eugenia Guitart, Maria Elvira Badaracco, Mariana Puntel, Fernando Pitossi, Jorge Correale, Juana Maria Pasquini
When disrupted, iron homeostasis negatively impacts oligodendrocyte (OLG) differentiation and impairs myelination. To better understand myelin formation and OLG maturation, in vivo and in vitro studies were conducted to evaluate the effect of iron deficiency (ID) not only on OLG maturation but also on astrocytes (AST) and microglial cells (MG). In vivo experiments in an ID model were carried out to describe maturational events during OLG and AST development and the reactive profile of MG during myelination when iron availability is lower than normal...
January 14, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28092083/role-of-dopamine-d2-d3-receptors-in-development-plasticity-and-neuroprotection-in-human-ipsc-derived-midbrain-dopaminergic-neurons
#3
Federica Bono, Paola Savoia, Adele Guglielmi, Massimo Gennarelli, Giovanna Piovani, Sandra Sigala, Damiana Leo, Stefano Espinoza, Raul R Gainetdinov, Paola Devoto, PierFranco Spano, Cristina Missale, Chiara Fiorentini
The role of dopamine D2 and D3 receptors (D2R/D3R), located on midbrain dopaminergic (DA) neurons, in the regulation of DA synthesis and release and in DA neuron homeostasis has been extensively investigated in rodent animal models. By contrast, the properties of D2R/D3R in human DA neurons have not been elucidated yet. On this line, the use of human-induced pluripotent stem cells (hiPSCs) for producing any types of cells has offered the innovative opportunity for investigating the human neuronal phenotypes at the molecular levels...
January 14, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28091913/regenerative-potential-of-stem-and-progenitor-cells-from-ischemic-testes-of-c57bl-6-mice-in-culture-and-in-the-model-of-spermatogenesis-suppression-caused-by-busulfan
#4
E G Skurikhin, A V Pakhomova, O V Pershina, L A Ermolaeva, N N Ermakova, V A Krupin, E S Pan, A I Kudryashova, O Yu Rybalkina, V V Zhdanov, V E Goldberg, A M Dygai
The regenerative potential of stem and progenitor cells from ischemic testes of C57Bl/6 mice was studied in vitro (cell culture) and in vivo (mouse model of busulfan-induced suppression of spermatogenesis). Spermatogonial stem cells with phenotypes CD117(-)CD90(+) and CD51(-)CD24(+)CD52(+) from ischemic testes demonstrated 33-fold and 7-fold increments of cell mass and generated colonies in vitro. Epithelial (CD45(-)CD31(-)Sca-1(+)CD49f(+)) and endothelial (CD45(-)CD31(+)) precursors exhibited lower self-renewal capacity...
January 14, 2017: Bulletin of Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28090703/differentiation-of-islet-progenitors-regulated-by-nicotinamide-into-transcriptome-verified-%C3%AE-cells-that-ameliorate-diabetes
#5
Fang-Xu Jiang, Kevin Li, Michael Archer, Munish Mehta, Emma Jamieson, Adrian Charles, Jan E Dickinson, Masahito Matsumoto, Grant Morahan
Developmental stage-specific differentiation of stem or progenitor cells into safe and functional cells is of fundamental importance in regenerative medicine, including β-cell replacement. However, the differentiation of islet progenitor cells (IPCs) into insulin-secreting β cells remains elusive. Here, we report that the multi-functional molecule nicotinamide (NIC) is a specific differentiation regulator of mouse IPCs. The differentiated cells regulated by NIC exhibited many characteristics of adult β cells, including ameliorating preclinical diabetes and a highly comparable transcriptome profile...
January 16, 2017: Stem Cells
https://www.readbyqxmd.com/read/28090699/modelling-irf8-deficient-human-hematopoiesis-and-dendritic-cell-development-with-engineered-ips-cells
#6
Stephanie Sontag, Malrun Förster, Jie Qin, Paul Wanek, Saskia Mitzka, Herdit M Schüler, Steffen Koschmieder, Stefan Rose-John, Kristin Seré, Martin Zenke
Human induced pluripotent stem (iPS) cells can differentiate into cells of all three germ layers, including hematopoietic stem cells and their progeny. Interferon regulatory factor 8 (IRF8) is a transcription factor, which acts in hematopoiesis as lineage determining factor for myeloid cells, including dendritic cells (DC). Autosomal recessive or dominant IRF8 mutations occurring in patients cause severe monocytic and DC immunodeficiency. To study IRF8 in human hematopoiesis we generated human IRF8-/- iPS cells and IRF8-/- embryonic stem (ES) cells using RNA guided CRISPR/Cas9n genome editing...
January 16, 2017: Stem Cells
https://www.readbyqxmd.com/read/28090691/peg3-pw1-is-a-marker-of-a-subset-of-vessel-associated-endothelial-progenitors
#7
Matteo Malinverno, Monica Corada, Luca Ferrarini, Luigi Formicola, Giovanna Marazzi, David Sassoon, Elisabetta Dejana
Vascular associated endothelial cell progenitors are still poorly studied and their role in the newly forming vasculature at embryonic or postnatal stage remains elusive. In the present work we first defined a set of genes highly expressed during embryo development and strongly down regulated in the adult mouse. In this group we then concentrated on the progenitor cell marker Peg3/PW1. By in vivo staining of the vasculature we found that only a subset of cells co-expressed endothelial markers and PW1. These cells were quite abundant in the embryo vasculature but declined in number at postnatal and adult stages...
January 16, 2017: Stem Cells
https://www.readbyqxmd.com/read/28090484/mesenchymal-stromal-cells-in-myeloid-malignancies
#8
REVIEW
Thomas Schroeder, Stefanie Geyh, Ulrich Germing, Rainer Haas
Myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) are clonal myeloid disorders characterized by hematopoietic insufficiency. As MDS and AML are considered to originate from genetic and molecular defects of hematopoietic stem and progenitor cells (HSPC), the main focus of research in this field has focused on the characterization of these cells. Recently, the contribution of BM microenvironment to the pathogenesis of myeloid malignancies, in particular MDS and AML has gained more interest. This is based on a better understanding of its physiological role in the regulation of hematopoiesis...
December 2016: Blood Research
https://www.readbyqxmd.com/read/28090290/shared-gene-expression-patterns-in-mesenchymal-progenitors-derived-from-lung-and-epidermis-in-pulmonary-arterial-hypertension-identifying-key-pathways-in-pulmonary-vascular-disease
#9
Christa Gaskill, Shennea Marriott, Sidd Pratap, Swapna Menon, Lora K Hedges, Joshua P Fessel, Jonathan A Kropski, DeWayne Ames, Lisa Wheeler, James E Loyd, Anna R Hemnes, Dennis R Roop, Dwight J Klemm, Eric D Austin, Susan M Majka
Rapid access to lung-derived cells from stable subjects is a major challenge in the pulmonary hypertension field, given the relative contraindication of lung biopsy. In these studies, we sought to demonstrate the importance of evaluating a cell type that actively participates in disease processes, as well as the potential to translate these findings to vascular beds in other nonlung tissues, in this instance perivascular skin mesenchymal cells (MCs). We utilized posttransplant or autopsy lung explant-derived cells (ABCG2-expressing mesenchymal progenitor cells [MPCs], fibroblasts) and skin-derived MCs to test the hypothesis that perivascular ABCG2 MPCs derived from pulmonary arterial hypertension (PAH) patient lung and skin would express a gene profile reflective of ongoing vascular dysfunction...
December 2016: Pulmonary Circulation
https://www.readbyqxmd.com/read/28089989/rhoa-regulates-actin-network-dynamics-during-apical-surface-emergence-in-multiciliated-epithelial-cells
#10
Jakub Sedzinski, Edouard Hannezo, Fan Tu, Maté Biro, John B Wallingford
Homeostatic replacement of epithelial cells from basal precursors is a multistep process involving progenitor cell specification, radial intercalation and, finally, apical surface emergence. Recent data demonstrate that actin-based pushing under the control of the formin protein Fmn1 drives apical emergence in nascent multiciliated epithelial cells (MCCs), but little else is known about this actin network or the control of Fmn1. Here, we explore the role of the small GTPase RhoA in MCC apical emergence. Disruption of RhoA function reduced the rate of apical surface expansion and decreased the final size of the apical domain...
January 15, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28089869/the-molecular-and-morphogenetic-basis-of-pancreas-organogenesis
#11
REVIEW
Hjalte List Larsen, Anne Grapin-Botton
The pancreas is an essential endoderm-derived organ that ensures nutrient metabolism via its endocrine and exocrine functions. Here we review the essential processes governing the embryonic and early postnatal development of the pancreas discussing both the mechanisms and molecules controlling progenitor specification, expansion and differentiation. We elaborate on how these processes are orchestrated in space and coordinated with morphogenesis. We draw mainly from experiments conducted in the mouse model but also from investigations in other model organisms, complementing a recent comprehensive review of human pancreas development (Jennings et al...
January 12, 2017: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/28089670/in%C3%A2-vitro-propagation-and-branching-morphogenesis-from-single-ureteric-bud%C3%A2-cells
#12
Shunsuke Yuri, Masaki Nishikawa, Naomi Yanagawa, Oak D Jo, Norimoto Yanagawa
A method to maintain and rebuild ureteric bud (UB)-like structures from UB cells in vitro could provide a useful tool for kidney regeneration. We aimed in our present study to establish a serum-free culture system that enables the expansion of UB progenitor cells, i.e., UB tip cells, and reconstruction of UB-like structures. We found that fibroblast growth factors or retinoic acid (RA) was sufficient for the survival of UB cells in serum-free condition, while the proliferation and maintenance of UB tip cells required glial cell-derived neurotrophic factor together with signaling from either WNT-β-catenin pathway or RA...
January 5, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28089669/exposure-to-gdnf-enhances-the-ability-of-enteric-neural-progenitors-to%C3%A2-generate-an-enteric-nervous-system
#13
Sonja J McKeown, Mitra Mohsenipour, Annette J Bergner, Heather M Young, Lincon A Stamp
Cell therapy is a promising approach to generate an enteric nervous system (ENS) and treat enteric neuropathies. However, for translation to the clinic, it is highly likely that enteric neural progenitors will require manipulation prior to transplantation to enhance their ability to migrate and generate an ENS. In this study, we examine the effects of exposure to several factors on the ability of ENS progenitors, grown as enteric neurospheres, to migrate and generate an ENS. Exposure to glial-cell-line-derived neurotrophic factor (GDNF) resulted in a 14-fold increase in neurosphere volume and a 12-fold increase in cell number...
January 6, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28089668/ebio-does-not-induce-cardiomyogenesis-in-human-pluripotent-stem-cells-but-modulates-cardiac-subtype-enrichment-by-lineage-selective-survival
#14
Monica Jara-Avaca, Henning Kempf, Michael Rückert, Diana Robles-Diaz, Annika Franke, Jeanne de la Roche, Martin Fischer, Daniela Malan, Philipp Sasse, Wladimir Solodenko, Gerald Dräger, Andreas Kirschning, Ulrich Martin, Robert Zweigerdt
Subtype-specific human cardiomyocytes (CMs) are valuable for basic and applied research. Induction of cardiomyogenesis and enrichment of nodal-like CMs was described for mouse pluripotent stem cells (mPSCs) in response to 1-ethyl-2-benzimidazolinone (EBIO), a chemical modulator of small-/intermediate-conductance Ca(2+)-activated potassium channels (SKs 1-4). Investigating EBIO in human pluripotent stem cells (PSCs), we have applied three independent differentiation protocols of low to high cardiomyogenic efficiency...
January 4, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28089145/effect-of-exercise-training-on-endothelial-function-in-heart-failure-patients-a-systematic-review-meta-analysis
#15
M J Pearson, N A Smart
OBJECTIVE: Endothelial dysfunction contributes to the development and progression of cardiovascular disease and heart failure (HF) and is associated with an increased risk of mortality. Flow-mediated dilation (FMD) is widely utilised to assess endothelial function and is improved with exercise training in heart failure patients. The aim of this meta-analysis is to quantify the effect of exercise training in patients with heart failure. BACKGROUND: A large number of studies now exist that have examined endothelial function in patients with heart failure...
December 28, 2016: International Journal of Cardiology
https://www.readbyqxmd.com/read/28088985/lymphocyte-generation-and-population-homeostasis-throughout-life
#16
REVIEW
Rolando E Yanes, Claire E Gustafson, Cornelia M Weyand, Jörg J Goronzy
Immune aging is a multi-faceted process that manifests as reduced competence to fight infections and malignant cells, as well as diminished tissue repair, unprovoked inflammation, and increased autoreactivity. The aging adaptive immune system, with its high complexity in functional cell subpopulations and diversity of B- and T-cell receptors, has to cope with the challenge of maintaining homeostasis while responding to exogenous stimuli and compensating for reduced generative capacity. With thymic involution, naïve T cells begin to function as quasi-stem cells and maintain the compartment through peripheral homeostatic proliferation that shapes the T-cell repertoire through peripheral selection and the activation of differentiation pathways...
January 2017: Seminars in Hematology
https://www.readbyqxmd.com/read/28088670/fibrin-hydrogels-induce-mixed-dorsal-ventral-spinal-neuron-identities-during-differentiation-of-human-induced-pluripotent-stem-cells
#17
John M Edgar, Meghan Robinson, Stephanie M Willerth
: We hypothesized that generating spinal motor neurons (sMNs) from human induced pluripotent stem cell (hiPSC)-derived neural aggregates (NAs) using a chemically-defined differentiation protocol would be more effective inside of 3D fibrin hydrogels compared to 2D poly-L-ornithine(PLO)/laminin-coated tissue culture plastic surfaces. We performed targeted RNA-Seq using next generation sequencing to determine the substrate-specific differences in gene expression that regulate cell phenotype...
January 11, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28088524/possible-roles-of-the-transcription-factor-nrf1-nfe2l1-in-neural-homeostasis-by-regulating-the-gene-expression-of-deubiquitinating-enzymes
#18
Hiroaki Taniguchi, Shota Okamuro, Misaki Kohji, Tsuyoshi Waku, Kaori Kubo, Atsushi Hatanaka, Yimeng Sun, A M Masudul Azad Chowdhury, Akiyoshi Fukamizu, Akira Kobayashi
The transcription factor Nrf1 (NFE2L1) maintains protein homeostasis (proteostasis) by regulating the gene expression of proteasome subunits in response to proteasome inhibition. The deletion of the Nrf1 gene in neural stem/progenitor cells causes severe neurodegeneration due to the accumulation of ubiquitinated proteins in Purkinje cells and motor neurons (Nrf1 NKO mice). However, the molecular mechanisms governing this neurodegenerative process remain unclear. We demonstrate herein that the loss of Nrf1 leads to the reduced gene expression of the deubiquitinating enzymes (DUBs) but not proteasome subunits in Nrf1 NKO mice between P7 and P18...
January 11, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28088466/teneurin-2-tenm2-deficiency-induces-ucp1-expression-in-differentiating-human-fat-cells
#19
D Tews, T Fromme, M Keuper, S M Hofmann, K M Debatin, M Klingenspor, M Wabitsch, P Fischer-Posovszky
Under certain conditions UCP1 expressing adipocytes arise in white adipose tissue depots of both mice and humans. It is still not fully understood whether these cells differentiate de novo from specific progenitor cells or if they transdifferentiate from mature white adipocytes. Performing expression pattern analysis comparing adipocyte progenitor cells from deep and subcutaneous neck adipose tissue, we recently identified teneurin-2 (TENM2) enriched in white adipocyte progenitor cells. Here we tested whether TENM2 deficiency in adipocyte progenitor cells would lead to a brown adipocyte phenotype...
January 11, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28088294/suitability-of-small-diagnostic-peripheral-blood-samples-for-cell-therapy-studies
#20
Coralea Stephanou, Panayiota Papasavva, Myria Zachariou, Petros Patsali, Marilena Epitropou, Petros Ladas, Ruba Al-Abdulla, Soteroulla Christou, Michael N Antoniou, Carsten W Lederer, Marina Kleanthous
BACKGROUND AIMS: Primary hematopoietic stem and progenitor cells (HSPCs) are key components of cell-based therapies for blood disorders and are thus the authentic substrate for related research. We propose that ubiquitous small-volume diagnostic samples represent a readily available and as yet untapped resource of primary patient-derived cells for cell- and gene-therapy studies. METHODS: In the present study we compare isolation and storage methods for HSPCs from normal and thalassemic small-volume blood samples, considering genotype, density-gradient versus lysis-based cell isolation and cryostorage media with different serum contents...
February 2017: Cytotherapy
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