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https://www.readbyqxmd.com/read/28938700/liver-cancers-with-stem-progenitor-cell-features-a-rare-chemotherapy-sensitive-malignancy
#1
Bruno Christian Köhler, Nina Waldburger, Kai Schlamp, Dirk Jäger, Karl Heinz Weiss, Henning Schulze-Bergkamen, Peter Schirmacher, Christoph Springfeld
Primary liver tumors are a heterogeneous group of malignancies. Besides classical hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC), combined and intermediate forms of liver cancer exist and can express stem-cell markers like nuclear cell adhesion molecule (NCAM-1/CD56), c-kit (CD117) or epithelial cell adhesion molecule (EpCAM) together with high proliferative activity. Liver tumors with progenitor-cell features are associated with an unfavorable prognosis, but the phenotype has not resulted in therapeutic consequences so far...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938435/the-role-of-sequential-bmp-signaling-in-directing-human-embryonic-stem-cells-to-bipotential-gonadal-cells
#2
Kirsi Sepponen, Karolina Lundin, Katri Knuus, Pia Väyrynen, Taneli Raivio, Juha S Tapanainen, Timo Tuuri
Context: Human gonads arise as a pair of epithelial ridges on the surface of intermediate mesoderm (IM)-derived mesonephros. Toxic environmental factors and mutations in various genes are known to disturb normal gonadal development, but due to a lack of suitable in vitro models, detailed studies characterizing the molecular basis of the observed defects have not been performed. Objective: Our objective was to establish an in vitro method for studying differentiation of bipotential gonadal progenitors using human embryonic stem cells (hESCs), and to investigate the role of bone morphogenetic protein (BMP) in gonadal differentiation...
August 29, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28899667/bhlh-o-proteins-balance-the-self-renewal-and-differentiation-of-drosophila-neural-stem-cells-by-regulating-earmuff-expression
#3
Xiaosu Li, Rui Chen, Sijun Zhu
Balancing self-renewal and differentiation of stem cells requires differential expression of self-renewing factors in two daughter cells generated from the asymmetric division of the stem cells. In Drosophila type II neural stem cell (or neuroblast, NB) lineages, the expression of the basic helix-loop-helix-Orange (bHLH-O) family proteins, including Deadpan (Dpn) and E(spl) proteins, is required for maintaining the self-renewal and identity of type II NBs, whereas the absence of these self-renewing factors is essential for the differentiation of intermediate neural progenitors (INPs) generated from type II NBs...
September 9, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28855626/dual-roles-of-a%C3%AE-in-proliferative-processes-in-an-amyloidogenic-model-of-alzheimer-s-disease
#4
David Baglietto-Vargas, Elisabeth Sánchez-Mejias, Victoria Navarro, Sebastián Jimenez, Laura Trujillo-Estrada, Angela Gómez-Arboledas, Maria Sánchez-Mico, Raquel Sánchez-Varo, Marisa Vizuete, José Carlos Dávila, José Manuel García-Verdugo, Javier Vitorica, Antonia Gutierrez
Alzheimer's disease is a major neurodegenerative disorder that leads to severe cognitive deficits in the elderly population. Over the past two decades, multiple studies have focused on elucidating the causative factors underlying memory defects in Alzheimer's patients. In this regard, new evidence linking Alzheimer's disease-related pathology and neuronal stem cells suggests that hippocampal neurogenesis impairment is an important factor underlying these cognitive deficits. However, because of conflicting results, the impact of Aβ pathology on neurogenesis/gliogenesis remains unclear...
August 30, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28844904/germ-cell-cysts-and-simultaneous-sperm-and-oocyte-production-in-a-hermaphroditic-nematode
#5
Caitlin M McCaig, Xiaoxue Lin, Maureen Farrell, Kathryn Rehain-Bell, Diane C Shakes
Studies of gamete development in the self-fertile hermaphrodites of Caenorhabditis elegans have significantly contributed to our understanding of fundamental developmental mechanisms. However, evolutionary transitions from outcrossing males and females to self-fertile hermaphrodites have convergently evolved within multiple nematode sub-lineages, and whether the C. elegans pattern of self-fertile hermaphroditism and gamete development is representative remains largely unexplored. Here we describe a pattern of sperm production in the trioecious (male/female/hermaphrodite) nematode Rhabditis sp...
August 24, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28827097/unipotent-progenitors-contribute-to-the-generation-of-sensory-cell-types-in-the-nervous-system-of-the-cnidarian-nematostella-vectensis
#6
Henriette Busengdal, Fabian Rentzsch
Nervous systems often consist of a large number of different types of neurons which are generated from neural stem and progenitor cells by a series of symmetric and asymmetric divisions. The origin and early evolution of these neural progenitor systems is not well understood. Here we use a cnidarian model organism, Nematostella vectensis, to gain insight into the generation of neural cell type diversity in a non-bilaterian animal. We identify NvFoxQ2d as a transcription factor that is expressed in a population of spatially restricted, proliferating ectodermal cells that are derived from NvSoxB(2)-expressing neural progenitor cells...
August 18, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28819363/combined-analysis-of-endothelial-hematopoietic-and-mesenchymal-stem-cell-compartments-shows-simultaneous-but-independent-effects-of-age-and-heart-disease
#7
Carine Ghem, Lucinara Dadda Dias, Roberto Tofani Sant'Anna, Renato A K Kalil, Melissa Markoski, Nance Beyer Nardi
Clinical trials using stem cell therapy for heart diseases have not reproduced the initial positive results obtained with animal models. This might be explained by a decreased regenerative capacity of stem cells collected from the patients. This work aimed at the simultaneous investigation of endothelial stem/progenitor cells (EPCs), mesenchymal stem/progenitor cells (MSCs), and hematopoietic stem/progenitor cells (HSCs) in sternal bone marrow samples of patients with ischemic or valvular heart disease, using flow cytometry and colony assays...
2017: Stem Cells International
https://www.readbyqxmd.com/read/28808228/loss-of-usp9x-disrupts-cell-adhesion-and-components-of-the-wnt-and-notch-signaling-pathways-in-neural-progenitors
#8
Susitha Premarathne, Mariyam Murtaza, Nicholas Matigian, Lachlan A Jolly, Stephen A Wood
Development of neural progenitors depends upon the coordination of appropriate intrinsic responses to extrinsic signalling pathways. Here we show the deubiquitylating enzyme, Usp9x regulates components of both intrinsic and extrinsic fate determinants. Nestin-cre mediated ablation of Usp9x from embryonic neural progenitors in vivo resulted in a transient disruption of cell adhesion and apical-basal polarity and, an increased number and ectopic localisation of intermediate neural progenitors. In contrast to other adhesion and polarity proteins, levels of β-catenin protein, especially S33/S37/T41 phospho-β-catenin, were markedly increased in Usp9x (-/Y) embryonic cortices...
August 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28798065/self-organization-process-in-newborn-skin-organoid-formation-inspires-strategy-to-restore-hair-regeneration-of-adult-cells
#9
Mingxing Lei, Linus J Schumacher, Yung-Chih Lai, Wen-Tau Juan, Chao-Yuan Yeh, Ping Wu, Ting-Xin Jiang, Ruth E Baker, Randall Bruce Widelitz, Li Yang, Cheng-Ming Chuong
Organoids made from dissociated progenitor cells undergo tissue-like organization. This in vitro self-organization process is not identical to embryonic organ formation, but it achieves a similar phenotype in vivo. This implies genetic codes do not specify morphology directly; instead, complex tissue architectures may be achieved through several intermediate layers of cross talk between genetic information and biophysical processes. Here we use newborn and adult skin organoids for analyses. Dissociated cells from newborn mouse skin form hair primordia-bearing organoids that grow hairs robustly in vivo after transplantation to nude mice...
August 22, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28790015/retinoic-acid-controls-early-neurogenesis-in-the-developing-mouse-cerebral-cortex
#10
Carole Haushalter, Laure Asselin, Valérie Fraulob, Pascal Dollé, Muriel Rhinn
A tight regulation of neuron production is required to generate a functional cerebral cortex and is achieved by a proper balance between proliferation and differentiation of progenitor cells. Though the vitamin A (retinol) active derivative retinoic acid (RA) has been implicated as one of the signals acting during mammalian forebrain neurogenesis, its function at the onset of neurogenesis as well as during establishment of cortical layers and neuronal subtypes remains elusive. One limitation is that murine mutants for genes encoding key enzymes involved in RA synthesis die during early embryonic development...
August 5, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28781964/loss-of-suppressor-of-fused-in-mid-corticogenesis-leads-to-the-expansion-of-intermediate-progenitors
#11
Odessa R Yabut, Hui Xuan Ng, Gloria Fernandez, Keejung Yoon, Jeremy Kuhn, Samuel J Pleasure
Neural progenitors in the embryonic neocortex must be tightly regulated in order to generate the correct number and projection neuron subtypes necessary for the formation of functional neocortical circuits. In this study, we show that the intracellular protein Suppressor of Fused (Sufu) regulates the proliferation of intermediate progenitor (IP) cells at later stages of corticogenesis to affect the number of Cux1+ upper layer neurons in the postnatal neocortex. This correlates with abnormal levels of the repressor form of Gli3 (Gli3R) and the ectopic expression of Patched 1 (Ptch1), a Sonic Hedgehog (Shh) target gene...
December 2016: Journal of Developmental Biology
https://www.readbyqxmd.com/read/28768907/upregulated-heme-biosynthesis-an-exploitable-vulnerability-in-mycn-driven-leukemogenesis
#12
Yu Fukuda, Yao Wang, Shangli Lian, John Lynch, Shinjiro Nagai, Bruce Fanshawe, Ayten Kandilci, Laura J Janke, Geoffrey Neale, Yiping Fan, Brian P Sorrentino, Martine F Roussel, Gerard Grosveld, John D Schuetz
The increased heme biosynthesis long observed in leukemia was previously of unknown significance. Heme, synthesized from porphyrin precursors, plays a central role in oxygen metabolism and mitochondrial function, yet little is known about its role in leukemogenesis. Here, we show increased expression of heme biosynthetic genes, including UROD, only in pediatric AML samples that have high MYCN expression. High expression of both UROD and MYCN predicts poor overall survival and unfavorable outcomes in adult AML...
August 3, 2017: JCI Insight
https://www.readbyqxmd.com/read/28765330/genome-stability-by-dna-polymerase-%C3%AE-in-neural-progenitors-contributes-to-neuronal-differentiation-in-cortical-development
#13
Kohei Onishi, Akiko Uyeda, Mitsuhiro Shida, Teruyoshi Hirayama, Takeshi Yagi, Nobuhiko Yamamoto, Noriyuki Sugo
DNA repair is crucial for genome stability in the developing cortex, as somatic de novo mutations cause neurological disorders. However, how DNA repair contributes to neuronal development is largely unknown. To address this issue, we studied the spatiotemporal roles of DNA polymerase β (Polβ), a key enzyme in DNA base excision repair (BER) pathway, in the developing cortex using distinct forebrain-specific conditional knockout mice, Emx1-Cre/Polβ(fl/fl) and Nex-Cre/Polβ(fl/fl) mice. Polβ expression was absent in both neural progenitors and postmitotic neurons in Emx1-Cre/Polβ(fl/fl) mice, while only postmitotic neurons lacked Polβ expression in Nex-Cre/Polβ(fl/fl) mice...
August 1, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28763796/the-metabolic-regulator-mtorc1-controls-terminal-myeloid-differentiation
#14
Pui Y Lee, David B Sykes, Sarah Ameri, Demetrios Kalaitzidis, Julia F Charles, Nathan Nelson-Maney, Kevin Wei, Pierre Cunin, Allyn Morris, Astrid E Cardona, David E Root, David T Scadden, Peter A Nigrovic
Monocytes are derived from hematopoietic stem cells through a series of intermediate progenitor stages, but the factors that regulate this process are incompletely defined. Using a Ccr2/Cx3cr1 dual-reporter system to model murine monocyte ontogeny, we conducted a small-molecule screen that identified an essential role of mechanistic target of rapamycin complex 1 (mTORC1) in the development of monocytes and other myeloid cells. Confirmatory studies using mice with inducible deletion of the mTORC1 component Raptor demonstrated absence of mature circulating monocytes, as well as disruption in neutrophil and dendritic cell development, reflecting arrest of terminal differentiation at the granulocyte-monocyte progenitor stage...
May 26, 2017: Science Immunology
https://www.readbyqxmd.com/read/28759657/hiv-1-infection-depletes-human-cd34-cd38-hematopoietic-progenitor-cells-via-pdc-dependent-mechanisms
#15
Guangming Li, Juanjuan Zhao, Liang Cheng, Qi Jiang, Sheng Kan, Enqiang Qin, Bo Tu, Xin Zhang, Liguo Zhang, Lishan Su, Zheng Zhang
Chronic human immunodeficiency virus-1 (HIV-1) infection in patients leads to multi-lineage hematopoietic abnormalities or pancytopenia. The deficiency in hematopoietic progenitor cells (HPCs) induced by HIV-1 infection has been proposed, but the relevant mechanisms are poorly understood. We report here that both human CD34+CD38- early and CD34+CD38+ intermediate HPCs were maintained in the bone marrow (BM) of humanized mice. Chronic HIV-1 infection preferentially depleted CD34+CD38- early HPCs in the BM and reduced their proliferation potential in vivo in both HIV-1-infected patients and humanized mice, while CD34+CD38+ intermediate HSCs were relatively unaffected...
July 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28757165/an-efficient-platform-for-astrocyte-differentiation-from-human-induced-pluripotent-stem-cells
#16
Julia Tcw, Minghui Wang, Anna A Pimenova, Kathryn R Bowles, Brigham J Hartley, Emre Lacin, Saima I Machlovi, Rawan Abdelaal, Celeste M Karch, Hemali Phatnani, Paul A Slesinger, Bin Zhang, Alison M Goate, Kristen J Brennand
Growing evidence implicates the importance of glia, particularly astrocytes, in neurological and psychiatric diseases. Here, we describe a rapid and robust method for the differentiation of highly pure populations of replicative astrocytes from human induced pluripotent stem cells (hiPSCs), via a neural progenitor cell (NPC) intermediate. We evaluated this protocol across 42 NPC lines (derived from 30 individuals). Transcriptomic analysis demonstrated that hiPSC-astrocytes from four individuals are highly similar to primary human fetal astrocytes and characteristic of a non-reactive state...
August 8, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28717251/transdifferentiated-human-vascular-smooth-muscle-cells-are-a-new-potential-cell-source-for-endothelial-regeneration
#17
Xuechong Hong, Andriana Margariti, Alexandra Le Bras, Laureen Jacquet, Wei Kong, Yanhua Hu, Qingbo Xu
Endothelial dysfunction is widely implicated in cardiovascular pathological changes and development of vascular disease. In view of the fact that the spontaneous endothelial cell (EC) regeneration is a slow and insufficient process, it is of great interest to explore alternative cell sources capable of generating functional ECs. Vascular smooth muscle cell (SMC) composes the majority of the vascular wall and retains phenotypic plasticity in response to various stimuli. The aim of this study is to test the feasibility of the conversion of SMC into functional EC through the use of reprogramming factors...
July 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28716722/dynamics-of-proliferative-and-quiescent-stem-cells-in-liver-homeostasis-and-injury
#18
Wanlu Cao, Kan Chen, Michiel Bolkestein, Yuebang Yin, Monique M A Verstegen, Marcel J C Bijvelds, Wenshi Wang, Nesrin Tuysuz, Derk Ten Berge, Dave Sprengers, Herold J Metselaar, Luc J W van der Laan, Jaap Kwekkeboom, Ron Smits, Maikel P Peppelenbosch, Qiuwei Pan
BACKGROUND & AIMS: Adult liver stem cells are usually maintained in a quiescent/slow-cycling state. However, a proliferative population, marked by leucine-rich repeat-containing G-protein coupled receptor 5 (LGR5), was recently identified as an important liver stem cell population. We aimed to investigate the dynamics and functions of proliferative and quiescent stem cells in healthy and injured livers. METHODS: We studied LGR5-positive stem cells using diphtheria toxin receptor and green fluorescent protein (GFP) knockin mice...
July 14, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28709146/liver-cancers-with-stem-progenitor-cell-features-a-rare-chemotherapy-sensitive-malignancy
#19
Bruno Christian Köhler, Nina Waldburger, Kai Schlamp, Dirk Jäger, Karl Heinz Weiss, Henning Schulze-Bergkamen, Peter Schirmacher, Christoph Springfeld
Primary liver tumors are a heterogeneous group of malignancies. Besides classical hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC), combined and intermediate forms of liver cancer exist and can express stem-cell markers like nuclear cell adhesion molecule (NCAM-1/CD56), c-kit (CD117) or epithelial cell adhesion molecule (EpCAM) together with high proliferative activity. Liver tumors with progenitor-cell features are associated with an unfavorable prognosis, but the phenotype has not resulted in therapeutic consequences so far...
June 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28690640/wdr62-regulates-early-neural-and-glial-progenitor-specification-of-human-pluripotent-stem-cells
#20
Abdullah J Alshawaf, Ana Antonic, Efstratios Skafidas, Dominic Chi-Hung Ng, Mirella Dottori
Mutations in WD40-repeat protein 62 (WDR62) are commonly associated with primary microcephaly and other developmental cortical malformations. We used human pluripotent stem cells (hPSC) to examine WDR62 function during human neural differentiation and model early stages of human corticogenesis. Neurospheres lacking WDR62 expression showed decreased expression of intermediate progenitor marker, TBR2, and also glial marker, S100β. In contrast, inhibition of c-Jun N-terminal kinase (JNK) signalling during hPSC neural differentiation induced upregulation of WDR62 with a corresponding increase in neural and glial progenitor markers, PAX6 and EAAT1, respectively...
2017: Stem Cells International
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