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Liankai Chi, Beibei Fan, Kunshan Zhang, Yanhua Du, Zhongliang Liu, Yujiang Fang, Zhenyu Chen, Xudong Ren, Xiangjie Xu, Cizhong Jiang, Siguang Li, Lin Ma, Liang Gao, Ling Liu, Xiaoqing Zhang
Embryoid body (EB) formation and adherent culture (AD) paradigms are equivalently thought to be applicable for neural specification of human pluripotent stem cells. Here, we report that sonic hedgehog-induced ventral neuroprogenitors under EB conditions are fated to medial ganglionic eminence (MGE), while the AD cells mostly adopt a floor-plate (FP) fate. The EB-MGE later on differentiates into GABA and cholinergic neurons, while the AD-FP favors dopaminergic neuron specification. Distinct developmental, metabolic, and adhesion traits in AD and EB cells may potentially account for their differential patterning potency...
September 27, 2016: Stem Cell Reports
Hang Yao, Priti Azad, Huiwen W Zhao, Juan Wang, Orit Poulsen, Beatriz C Freitas, Alysson R Muotri, Gabriel G Haddad
The sodium bicarbonate co-transporter (NBC) is the major bicarbonate-dependent acid-base transporter in mammalian astrocytes and has been implicated in ischemic brain injury. A malfunction of astrocytes could have great impact on the outcome of stroke due to their participation in the formation of blood-brain barrier, synaptic transmission, and electrolyte balance in the human brain. Nevertheless, the role of NBC in the ischemic astrocyte death has not been well understood. In this work, we obtained skin biopsies from healthy human subjects and had their fibroblasts grown in culture and reprogrammed into human-induced pluripotent stem cells (hiPSCs)...
October 4, 2016: Neuroscience
Maryam Nazm Bojnordi, Hossein Azizi, Thomas Skutella, Mansoureh Movahedin, Fereshteh Pourabdolhossein, Amir Shojaei, Hatef Ghasemi Hamidabadi
Transplantation of embryonic stem cells (ESCs) is a promising therapeutic approach for the treatment of neurodegenerative diseases. However, ESCs are not usable clinically due to immunological and ethical limitations. The identification of an alternative safe cell source opens novel options via autologous transplantation in neuro-regeneration circumventing these problems. Here, we examined the neurogenic capacity of embryonic stem-like cells (ES-like cells) derived from the testis using neural growth factor inducers and utilized them to generate functional mature neurons...
September 19, 2016: Molecular Neurobiology
HyeonJu Kim, Ying Wei, Ji Yong Lee, Yue Wu, Yi Zheng, Michael A Moskowitz, John W Chen
The relationship between inflammation and neurogenesis in stroke is currently not well understood. Focal ischemia enhances cell proliferation and neurogenesis in the neurogenic regions, including the subventricular zone (SVZ), dentate gyrus, as well as the non-neurogenic striatum, and cortex in the ischemic hemisphere. Myeloperoxidase (MPO) is a potent oxidizing enzyme secreted during inflammation by activated leukocytes, and its enzymatic activity is highly elevated after stroke. In this study, we investigated whether the inhibition of MPO activity by a specific irreversible inhibitor, 4-aminobenzoic acid hydrazide (ABAH) (MPO(-/-) mice) can increase neurogenesis after transient middle cerebral artery occlusion in mice...
November 2016: Journal of Pharmacology and Experimental Therapeutics
Andréa Geoffroy, Racha Kerek, Grégory Pourié, Déborah Helle, Jean-Louis Guéant, Jean-Luc Daval, Carine Bossenmeyer-Pourié
The micronutrients folate and vitamin B12 are essential for the proper development of the central nervous system, and their deficiency during pregnancy has been associated with a wide range of disorders. They act as methyl donors in the one-carbon metabolism which critically influences epigenetic mechanisms. In order to depict further underlying mechanisms, we investigated the role of let-7 and miR-34, two microRNAs regulated by methylation, on a rat model of maternal deficiency. In several countries, public health policies recommend periconceptional supplementation with folic acid...
August 17, 2016: Molecular Neurobiology
Ranad Shaheen, Amal Hashem, Ghada M H Abdel-Salam, Fatima Al-Fadhli, Nour Ewida, Fowzan S Alkuraya
Primary microcephaly is a clinical phenotype in which the head circumference is significantly reduced at birth due to abnormal brain development, primarily at the cortical level. Despite the marked genetic heterogeneity, most primary microcephaly-linked genes converge on mitosis regulation. Two consanguineous families segregating the phenotype of severe primary microcephaly, spasticity and failure to thrive had overlapping autozygomes in which exome sequencing identified homozygous splicing variants in CIT that segregate with the phenotype within each family...
October 2016: Human Genetics
I-Seul Joe, Goang-Won Cho
Increased intracellular cyclic adenosine monophosphate (cAMP) can promote axonal elongation and facilitate neuronal repair, while decreased cAMP is associated with losses in neuronal regenerative capacity. Rolipram, which upregulates intracellular cAMP by blocking phosphodiesterase-4 (PDE4) enzyme activity, can mitigate diverse neurological disorders. In this study, we investigated whether rolipram induces neuronal differentiation of human bone marrow-mesenchymal stem cells (hBM-MSCs). Rolipram-treated MSCs (Roli-MSCs) had significantly increased expression of the neuroprogenitor proteins Nestin, Musashi, GFAP, and Sox-2...
August 2016: Cellular Reprogramming
Bor Luen Tang
Zika virus (ZIKV) infection has been associated with congenital microcephaly and peripheral neuropathy. The ongoing epidemic has triggered swift responses in the scientific community, and a number of recent reports have now confirmed a causal relationship between ZIKV infection and birth defect. In particular, ZIKV has been shown to be capable of compromising and crossing the placental barrier and infect the developing fetal brain, resulting in the demise and functional impairment of neuroprogenitor cells critical for fetal cortex development...
September 2016: Archives of Microbiology
Marialaura Petroni, Giuseppe Giannini
DNA replication must be tightly regulated to ensure accurate duplication of the genome and its transfer to the daughter cells. When these regulatory mechanisms fail, replicative stress and DNA damage ensue, eventually leading to cell cycle inhibition or cell death. We have recently uncovered that MYCN-dependent expansion of neuroprogenitor cells is accompanied by replication stress, which is restrained by the MRN complex, a direct transcriptional target of the MYCN proto-oncogene.
March 2016: Molecular & Cellular Oncology
Nady El Hajj, Marcus Dittrich, Julia Böck, Theo F J Kraus, Indrajit Nanda, Tobias Müller, Larissa Seidmann, Tim Tralau, Danuta Galetzka, Eberhard Schneider, Thomas Haaf
Using Illumina 450K arrays, 1.85% of all analyzed CpG sites were significantly hypermethylated and 0.31% hypomethylated in fetal Down syndrome (DS) cortex throughout the genome. The methylation changes on chromosome 21 appeared to be balanced between hypo- and hyper-methylation, whereas, consistent with prior reports, all other chromosomes showed 3-11 times more hyper- than hypo-methylated sites. Reduced NRSF/REST expression due to upregulation of DYRK1A (on chromosome 21q22.13) and methylation of REST binding sites during early developmental stages may contribute to this genome-wide excess of hypermethylated sites...
August 2, 2016: Epigenetics: Official Journal of the DNA Methylation Society
Xiaoqian Liu, Zhong-Wei Zhou, Zhao-Qi Wang
Microcephalin (MCPH1) is identified as being responsible for the neurodevelopmental disorder primary microcephaly type 1, which is characterized by a smaller-than-normal brain size and mental retardation. MCPH1 has originally been identified as an important regulator of telomere integrity and of cell cycle control. Genetic and cellular studies show that MCPH1 controls neurogenesis by coordinating the cell cycle and the centrosome cycle and thereby regulating the division mode of neuroprogenitors to prevent the exhaustion of the progenitor pool and thereby microcephaly...
July 2016: Acta Biochimica et Biophysica Sinica
Carolina Paola García, Guillermo Agustín Videla Richardson, Nicolás Alexis Dimopoulos, Damián Darío Fernandez Espinosa, Santiago Gabriel Miriuka, Gustavo Emilio Sevlever, Leonardo Romorini, María Elida Scassa
Human embryonic stem cells (hESCs) are hypersensitive to genotoxic stress and display lower survival ability relative to their differentiated progeny. Herein, we attempted to investigate the source of this difference by comparing the DNA damage responses triggered by the topoisomerase I inhibitor camptothecin, in hESCs, human induced pluripotent stem cells (hiPSCs) and hESCs-derived neuroprogenitors (NP). We observed that upon camptothecin exposure pluripotent stem cells underwent apoptosis more swiftly and at a higher rate than differentiated cells...
2016: PloS One
Radu Boitor, Faris Sinjab, Stephanie Strohbuecker, Virginie Sottile, Ioan Notingher
Raman micro-spectroscopy (RMS) is a non-invasive technique for imaging live cells in vitro. However, obtaining quantitative molecular information from Raman spectra is difficult because the intensity of a Raman band is proportional to the number of molecules in the sampled volume, which depends on the local molecular concentration and the thickness of the cell. In order to understand these effects, we combined RMS with atomic force microscopy (AFM), a technique that can measure accurately the thickness profile of the cells...
June 23, 2016: Faraday Discussions
Xinde Zheng, Leah Boyer, Mingji Jin, Yongsung Kim, Weiwei Fan, Cedric Bardy, Travis Berggren, Ronald M Evans, Fred H Gage, Tony Hunter
mTOR inhibition is beneficial in neurodegenerative disease models and its effects are often attributable to the modulation of autophagy and anti-apoptosis. Here, we report a neglected but important bioenergetic effect of mTOR inhibition in neurons. mTOR inhibition by rapamycin significantly preserves neuronal ATP levels, particularly when oxidative phosphorylation is impaired, such as in neurons treated with mitochondrial inhibitors, or in neurons derived from maternally inherited Leigh syndrome (MILS) patient iPS cells with ATP synthase deficiency...
2016: ELife
Ashley M Driver, Lisa E Kratz, Richard I Kelley, Rolf W Stottmann
We previously reported a mutation in the cholesterol biosynthesis gene, hydroxysteroid (17-beta) dehydrogenase 7 (Hsd17b7(rudolph)), that results in striking embryonic forebrain dysgenesis. Here we describe abnormal patterns of neuroprogenitor proliferation in the mutant forebrain, namely, a decrease in mitotic cells within the ventricular zone (VZ) and an increase through the remainder of the cortex by E11.5. Further evidence suggests mutant cells undergo abnormal interkinetic nuclear migration (IKNM). Furthermore, intermediate progenitors are increased at the expense of apical progenitors by E12...
July 2016: Neurobiology of Disease
Jie Lu, Monika Mccarter, Gewei Lian, Giuseppe Esposito, Elena Capoccia, Laurent C Delli-Bovi, Jonathan Hecht, Volney Sheen
Down syndrome (DS) is caused by a triplication of chromosome 21 (HSA21). Increased oxidative stress, decreased neurogenesis and synaptic dysfunction from HSA21 gene overexpression are thought to cause mental retardation, dementia and seizure in this disorder. Recent epigenetic studies have raised the possibility that DNA methylation has significant effects on DS neurodevelopment. Here, we performed methylome profiling in normal and DS fetal cortices and observed a significant hypermethylation in ∼4% of probes in the DS samples compared with age-matched normals...
May 1, 2016: Human Molecular Genetics
Wei-Bin Shen, Dennis E Vaccaro, Paul S Fishman, Ernest V Groman, Paul Yarowsky
This is the first report of the synthesis of a new nanoparticle, sans iron oxide rhodamine B (SIRB), an example of a new class of nanoparticles. SIRB is designed to provide all of the cell labeling properties of the ultrasmall superparamagnetic iron oxide (USPIO) nanoparticle Molday ION Rhodamine B (MIRB) without containing the iron oxide core. MIRB was developed to label cells and allow them to be tracked by MRI or to be manipulated by magnetic gradients. SIRB possesses a similar size, charge and cross-linked dextran coating as MIRB...
May 2016: Contrast Media & Molecular Imaging
Mina Desai, Guang Han, Michael G Ross
Maternal overnutrition results in programmed offspring obesity, mediated in part, by hyperphagia. This is remarkably similar to the effects of maternal undernutrition on offspring hyperphagia and obesity. In view of the marked differences in the energy environment of the over and under-nutrition exposures, we studied the expression of select epigenetic modifiers associated with energy imbalance including neurogenic factors and appetite/satiety neuropeptides which are indicative of neurogenic differentiation...
April 1, 2016: Appetite
Nicky Helsen, Yannick Debing, Jan Paeshuyse, Kai Dallmeier, Ruben Boon, Mar Coll, Pau Sancho-Bru, Christel Claes, Johan Neyts, Catherine M Verfaillie
BACKGROUND & AIMS: Yearly, approximately 20million people become infected with the hepatitis E virus (HEV) resulting in over 3million cases of acute hepatitis. Although HEV-mediated hepatitis is usually self-limiting, severe cases of fulminant hepatitis as well as chronic infections have been reported, resulting annually in an estimated 60,000 deaths. We studied whether pluripotent stem cell (PSC)-derived hepatocytes, mesodermal and/or neuroprogenitor cells support HEV replication. METHODS: Human PSC were differentiated towards hepatocyte-like cells, mesodermal cells and neuroprogenitors and subsequently infected with HEV...
March 2016: Journal of Hepatology
Aynun N Begum, Caleigh Guoynes, Jane Cho, Jijun Hao, Kabirullah Lutfy, Yiling Hong
Stem cell-based neuronal differentiation has provided a unique opportunity for disease modeling and regenerative medicine. Neurospheres are the most commonly used neuroprogenitors for neuronal differentiation, but they often clump in culture, which has always represented a challenge for neurodifferentiation. In this study, we report a novel method and defined culture conditions for generating sub-type or region-specific neurons from human embryonic and induced pluripotent stem cells derived neurosphere without any genetic manipulation...
November 2015: Stem Cell Research
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