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https://www.readbyqxmd.com/read/29160172/neural-differentiation-of-spheroids-derived-from-hipsc-msc-co-culture
#1
Liqing Song, Ang-Chen Tsai, Xuegang Yuan, Julie Bejoy, Sébastien Sart, Teng Ma, Yan Li
Organoids, the condensed 3-D tissues emerged at the early stage of organogenesis, are a promising approach to regenerate functional and vascularized organ mimics. While incorporation of heterotypic cell types such as human mesenchymal stem cells (hMSCs) and human induced pluripotent stem cells (hiPSCs) derived neural progenitors aid neural organ development, the interactions of secreted factors during neurogenesis have not been well understood. The objective of this study is to investigate the impact of the composition and structure of 3-D hybrid spheroids of hiPSCs and hMSCs on dorsal cortical differentiation and the secretion of extracellular matrices and trophic factors in vitro...
November 21, 2017: Tissue Engineering. Part A
https://www.readbyqxmd.com/read/29160151/extracellular-matrix-from-periodontal-ligament-cells-could-induce-the-differentiation-of-induced-pluripotent-stem-cells-to-periodontal-ligament-stem-cell-like-cells
#2
Sayuri Hamano, Atsushi Tomokiyo, Daigaku Hasegawa, Shinichiro Yoshida, Hideki Sugii, Hiromo Mitarai, Shoko Fujino, Naohisa Wada, Hidefumi Maeda
The periodontal ligament (PDL) plays an important role in anchoring teeth in the bone socket. Damage to the PDL, such as following severe inflammation, can be treated with a therapeutic strategy that uses stem cells derived from PDL tissue (PDLSCs), a strategy that has received intense scrutiny over the past decade. However, there is an insufficient number of PDLSCs within the PDL for treating such damage. Therefore, we sought to induce the differentiation of induced pluripotent stem (iPS) cells into PDLSCs as an initial step toward PDL therapy...
November 21, 2017: Stem Cells and Development
https://www.readbyqxmd.com/read/29158845/in-tether-chiral-center-induced-helical-peptide-modulators-target-p53-mdm2-mdmx-and-inhibit-tumor-growth-in-stem-like-cancer-cell
#3
Kuan Hu, Feng Yin, Mengyin Yu, Chengjie Sun, Jingxu Li, Yujie Liang, Wenjun Li, Mingsheng Xie, Yuanzhi Lao, Wei Liang, Zi-Gang Li
Inhibition of the interaction between p53 and MDM2/MDMX has attracted significant attention in anticancer therapy development. We designed a series of in-tether chiral center-induced helical stabilized peptides, among which MeR/PhR effectively reactivated p53. The activation of p53 inhibits cell proliferation and induces apoptosis in both the MCF-7 normal tumor cell line and the PA-1 pluripotent cancer cell line with only minimal cellular toxicity towards normal cells or cancer cell lines with p53 mutations...
2017: Theranostics
https://www.readbyqxmd.com/read/29158584/ketamine-enhances-structural-plasticity-in-mouse-mesencephalic-and-human-ipsc-derived-dopaminergic-neurons-via-ampar-driven-bdnf-and-mtor-signaling
#4
L Cavalleri, E Merlo Pich, M J Millan, C Chiamulera, T Kunath, P F Spano, G Collo
Among neurobiological mechanisms underlying antidepressant properties of ketamine, structural remodeling of prefrontal and hippocampal neurons has been proposed as critical. The suggested mechanism involves downstream activation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, which trigger mammalian target of rapamycin (mTOR)-dependent structural plasticity via brain-derived neurotrophic factor (BDNF) and protein neo-synthesis. We evaluated whether ketamine elicits similar molecular events in dopaminergic (DA) neurons, known to be affected in mood disorders, using a novel, translational strategy that involved mouse mesencephalic and human induced pluripotent stem cells-derived DA neurons...
November 21, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/29158583/patient-derived-ipscs-show-premature-neural-differentiation-and-neuron-type-specific-phenotypes-relevant-to-neurodevelopment
#5
E Yeh, D Q Dao, Z Y Wu, S M Kandalam, F M Camacho, C Tom, W Zhang, R Krencik, K A Rauen, E M Ullian, L A Weiss
Ras/MAPK pathway signaling is a major participant in neurodevelopment, and evidence suggests that BRAF, a key Ras signal mediator, influences human behavior. We studied the role of the mutation BRAF(Q257R), the most common cause of cardiofaciocutaneous syndrome (CFC), in an induced pluripotent stem cell (iPSC)-derived model of human neurodevelopment. In iPSC-derived neuronal cultures from CFC subjects, we observed decreased p-AKT and p-ERK1/2 compared to controls, as well as a depleted neural progenitor pool and rapid neuronal maturation...
November 21, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/29156730/generation-of-patient-specific-human-neural-stem-cells-from-niemann-pick-disease-type-c-patient-derived-fibroblasts
#6
Eun-Ah Sung, Kyung-Rok Yu, Ji-Hee Shin, Yoojin Seo, Hyung-Sik Kim, Myung Guen Koog, Insung Kang, Jae-Jun Kim, Byung-Chul Lee, Tae-Hoon Shin, Jin Young Lee, Seunghee Lee, Tae-Wook Kang, Soon Won Choi, Kyung-Sun Kang
Niemann-Pick disease type C (NPC) is a neurodegenerative and lysosomal lipid storage disorder, characterized by the abnormal accumulation of unesterified cholesterol and glycolipids, which is caused by mutations in the NPC1 genes. Here, we report the generation of human induced neural stem cells from NPC patient-derived fibroblasts (NPC-iNSCs) using only two reprogramming factors SOX2 and HMGA2 without going through the pluripotent state. NPC-iNSCs were stably expandable and differentiated into neurons, astrocytes, and oligodendrocytes...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156377/establishment-of-induced-pluripotent-stem-cell-line-zzui010-a-from-an-alzheimer-s-disease-patient-carrying-an-app-gene-mutation
#7
Zhilei Wang, Pei Zhang, Yanlin Wang, Changhe Shi, Na Jing, Huifang Sun, Jing Yang, Yutao Liu, Xuejun Wen, Jin Zhang, Shoutao Zhang, Yuming Xu
Alzheimer's disease (AD) is one of the most common neurodegenerative disorders. Previous studies have identified mutations in several genes, such as amyloid precursor protein (APP), presenilin-1 (PSEN1), and presenilin-2 (PSEN2), in patients with early-onset (<65years) familial AD. Recently, a patient with an APP gene mutation was identified; the dermal fibroblasts of the patient were obtained and a line of induced pluripotent stem cells (iPSCs) was successfully generated using the Sendai-virus (SeV) delivery system...
November 3, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/29156376/comparative-transcriptomic-analysis-of-endothelial-progenitor-cells-derived-from-umbilical-cord-blood-and-adult-peripheral-blood-implications-for-the-generation-of-induced-pluripotent-stem-cells
#8
Xiugong Gao, Jeffrey J Yourick, Robert L Sprando
Induced pluripotent stem cells (iPSCs) offer the potential to generate tissues with ethnic diversity enabling toxicity testing on selected populations. Recently, it has been reported that endothelial progenitor cells (EPCs) derived from umbilical cord blood (CB) or adult peripheral blood (PB) afford a practical and efficient cellular substrate for iPSC generation. However, differences between EPCs from different blood sources have rarely been studied. In the current study, we derived EPCs from blood mononuclear cells (MNCs) and reprogrammed EPCs into iPSCs...
November 7, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/29156239/examining-the-effects-of-alcohol-on-gabaa-receptor-mrna-expression-and-function-in-neural-cultures-generated-from-control-and-alcohol-dependent-donor-induced-pluripotent-stem-cells
#9
Richard Lieberman, Henry R Kranzler, Eric S Levine, Jonathan Covault
Factors influencing the development of alcohol-use disorder (AUD) are complex and heterogeneous. While animal models have been crucial to identifying actions of alcohol on neural cells, human-derived in vitro systems that reflect an individual's genetic background hold promise in furthering our understanding of the molecular and functional effects of alcohol exposure and the pathophysiology of AUD. In this report, we utilized induced pluripotent stem cell (iPSCs)-derived neural cell cultures obtained from healthy individuals (CTLs) and those with alcohol dependence (ADs) to 1) examine the effect of 21-day alcohol exposure on mRNA expression of three genes encoding GABAA receptor subunits (GABRA1, GABRG2, and GABRD) using quantitative PCR, and 2) examine the effect of acute and chronic alcohol exposure on GABA-evoked currents using whole-cell patch-clamp electrophysiology...
August 12, 2017: Alcohol
https://www.readbyqxmd.com/read/29155789/efficient-generation-and-editing-of-feeder-free-ipscs-from-human-pancreatic-cells-using-the-crispr-cas9-system
#10
Anjali Nandal, Barbara Mallon, Bhanu P Telugu
Embryonic and induced pluripotent stem cells can self-renew and differentiate into multiple cell types of the body. The pluripotent cells are thus coveted for research in regenerative medicine and are currently in clinical trials for eye diseases, diabetes, heart diseases, and other disorders. The potential to differentiate into specialized cell types coupled with the recent advances in genome editing technologies including the CRISPR/Cas system have provided additional opportunities for tailoring the genome of iPSC for varied applications including disease modeling, gene therapy, and biasing pathways of differentiation, to name a few...
November 8, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29155780/rapid-directed-differentiation-of-retinal-pigment-epithelial-cells-from-human-embryonic-or-induced-pluripotent-stem-cells
#11
Leah P Foltz, Dennis O Clegg
We describe a robust method to direct the differentiation of pluripotent stem cells into retinal pigment epithelial cells (RPE). The purpose of providing a detailed and thorough protocol is to clearly demonstrate each step and to make this readily available to researchers in the field. This protocol results in a homogenous layer of RPE with minimal or no manual dissection needed. The method presented here has been shown to be effective for induced pluripotent stem cells (iPSC) and human embryonic stem cells...
October 30, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29155716/evaluation-of-injury-induced-senescence-and-in-vivo-reprogramming-in-the-skeletal-muscle
#12
Coralie Cazin, Aurelie Chiche, Han Li
Cellular senescence is a stress response that is characterized by a stable cellular growth arrest, which is important for many physiological and pathological processes, such as cancer and ageing. Recently, senescence has also been implicated in tissue repair and regeneration. Therefore, it has become increasingly critical to identify senescent cells in vivo. Senescence-associated β-galactosidase (SA-β-Gal) assay is the most widely used assay to detect senescent cells both in culture and in vivo. This assay is based on the increased lysosomal contents in the senescent cells, which allows the histochemical detection of lysosomal β-galactosidase activity at suboptimum pH (6 or 5...
October 26, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29155325/promoter-activity-and-regulation-of-the-pou5f1-homolog-from-a-teleost-nile-tilapia
#13
Wei Jing, Huang Xiaohuan, Fan Zhenhua, Yang Zhuo, Da Fan, Tao Wenjing, Zhou Linyan, Wang Deshou
Mammalian POU5F1 (also known as OCT4) is an essential transcription factor that induces and controls stemness in the inner cell mass and embryonic stem (ES) cells. Its expression results from intricate regulatory networks involving its 5' upstream DNA elements and numerous transcription factors. Pou5f3, the ortholog of POU5F1, has been identified in non-mammalians including fish. However, little is known about the molecular mechanisms controlling its expression up to date. Here we report the promoter activity and regulation of Nile tilapia (Oreochromis niloticus) pou5f3 (Onpou5f3) in fish early-stage embryos and ES cells...
November 16, 2017: Gene
https://www.readbyqxmd.com/read/29155283/comparative-analysis-of-media-effects-on-human-induced-pluripotent-stem-cell-derived-cardiomyocytes-in-proarrhythmia-risk-assessment
#14
Derek Schocken, Jayna Stohlman, Jose Vicente, Dulciana Chan, Dakshesh Patel, Murali Krishna Matta, Vikram Patel, Mathew Brock, Daniel Millard, James Ross, David G Strauss, Ksenia Blinova
INTRODUCTION: Cardiotoxicity assessment using human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) forms a key component of the Comprehensive in Vitro Proarrhythmia Assay (CiPA). A potentially impactful factor on iPSC-CM testing is the presence of serum in the experimental media. Generally, serum-free media is used to most accurately reproduce "free" drug concentration. However, caution is needed; drug solubility and cardiomyocyte electrophysiology could be affected by media formulation, potentially impacting interpretation of drug-induced effects...
November 16, 2017: Journal of Pharmacological and Toxicological Methods
https://www.readbyqxmd.com/read/29155131/human-lung-epithelial-cell-cultures-for-analysis-of-inhaled-toxicants-lessons-learned-and-future-directions
#15
REVIEW
Pieter S Hiemstra, Gwendolynn Grootaers, Anne M van der Does, Cyrille A M Krul, Ingeborg M Kooter
The epithelium that covers the conducting airways and alveoli is a primary target for inhaled toxic substances, and therefore a focus in inhalation toxicology. The increasing concern about the use of animal models has stimulated the development of in vitro cell culture models for analysis of the biological effects of inhaled toxicants. However, the validity of the current in vitro models and their acceptance by regulatory authorities as an alternative to animal models is a reason for concern, and requires a critical review...
November 15, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/29154227/generation-of-integration-free-induced-pluripotent-stem-cell-line-njmui001-a-from-a-phenylketonuria-patient
#16
Tianhui Xu, Dong Liang, Jingjing Zhang, Xiuqing Ji, Huanran Hu, Yun Sun, Tao Jiang, Xia Wang, Ping Hu, Zhengfeng Xu
PKU is a prevalent type of inherited metabolic disease, caused by the defective phenylalanine metabolism. In most PKU cases, mutations in the PAH gene could be found. Dysfunction of this hepatic enzyme will lead to diverse clinical symptoms due to a failure in converting phenylalanine into tyrosine. Here, we report an integration-free human induced pluripotent stem cell line (NJMUi001-A) generated from peripheral blood mononuclear cells of a PKU patient by using Sendai virus. This iPS cell line has characteristics of pluripotent stem cells and can be used as a useful tool for the investigation of this inherited metabolic disease...
November 10, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/29154149/rar%C3%AE-2-dependent-signaling-represses-neuronal-differentiation-in-mouse-es-cells
#17
Sri L Kona, Amita Shrestha, Xiaoping Yi, Serenthia Joseph, Humberto Munoz Barona, Eduardo Martinez-Ceballos
Embryonic Stem (ES) cells are pluripotent cells that can be induced to differentiate into cells of all three lineages: mesoderm, endoderm, and ectoderm. In culture, ES cells can be differentiated into mature neurons by treatment with Retinoic Acid (RA) and this effect is mediated mainly through the activation of the RA nuclear receptors (RAR α, β, and γ), and their isoforms. However, little is known about the role played by specific RAR types on ES cell differentiation. Here, we found that treatment of ES cells with AC55649, an RARβ2 agonist, increased endodermal marker gene expression...
November 10, 2017: Differentiation; Research in Biological Diversity
https://www.readbyqxmd.com/read/29153991/serine-347-phosphorylation-by-jnks-negatively-regulates-oct4-protein-stability-in-mouse-embryonic-stem-cells
#18
Ki Beom Bae, Dong Hoon Yu, Kun Yeong Lee, Ke Yao, Joohyun Ryu, Do Young Lim, Tatyana A Zykova, Myoung Ok Kim, Ann M Bode, Zigang Dong
The POU transcription factor OCT4 is critical for maintaining the undifferentiated state of embryonic stem cells (ESCs) and generating induced pluripotent stem cells (iPSCs), but its precise mechanisms of action remain poorly understood. Here, we investigated the role of OCT4 phosphorylation in the biological functions of ESCs. We observed that c-Jun N-terminal kinases (JNKs) directly interacted with and phosphorylated OCT4 at serine 347, which inhibited the transcriptional activity of OCT4. Moreover, phosphorylation of OCT4 induced binding of FBXW8, which reduced OCT4 protein stability and enhanced its proteasomal degradation...
November 10, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/29153989/psen1-mutant-ipsc-derived-model-reveals-severe-astrocyte-pathology-in-alzheimer-s-disease
#19
Minna Oksanen, Andrew J Petersen, Nikolay Naumenko, Katja Puttonen, Šárka Lehtonen, Max Gubert Olivé, Anastasia Shakirzyanova, Stina Leskelä, Timo Sarajärvi, Matti Viitanen, Juha O Rinne, Mikko Hiltunen, Annakaisa Haapasalo, Rashid Giniatullin, Pasi Tavi, Su-Chun Zhang, Katja M Kanninen, Riikka H Hämäläinen, Jari Koistinaho
Alzheimer's disease (AD) is a common neurodegenerative disorder and the leading cause of cognitive impairment. Due to insufficient understanding of the disease mechanisms, there are no efficient therapies for AD. Most studies have focused on neuronal cells, but astrocytes have also been suggested to contribute to AD pathology. We describe here the generation of functional astrocytes from induced pluripotent stem cells (iPSCs) derived from AD patients with PSEN1 ΔE9 mutation, as well as healthy and gene-corrected isogenic controls...
November 12, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/29152164/mutations-in-rab39b-in-individuals-with-intellectual-disability-autism-spectrum-disorder-and-macrocephaly
#20
Marc Woodbury-Smith, Eric Deneault, Ryan K C Yuen, Susan Walker, Mehdi Zarrei, Giovanna Pellecchia, Jennifer L Howe, Ny Hoang, Mohammed Uddin, Christian R Marshall, Christina Chrysler, Ann Thompson, Peter Szatmari, Stephen W Scherer
Background: Autism spectrum disorder (ASD), a developmental disorder of early childhood onset, affects males four times more frequently than females, suggesting a role for the sex chromosomes. In this study, we describe a family with ASD in which a predicted pathogenic nonsense mutation in the X-chromosome gene RAB39B segregates with ASD phenotype. Methods: Clinical phenotyping, microarray, and whole genome sequencing (WGS) were performed on the five members of this family...
2017: Molecular Autism
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