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Naser Mobarra, Masoud Soleimani, Majid Ghayour-Mobarhan, Samaneh Safarpour, Gordon A Ferns, Reza Pakzad, Parvin Pasalar
A suitable alternative strategy for liver transplantation is the use of nanofibrous scaffolds together with stem cells. In this study, a random hybrid of poly-l-lactic acid (PLLA) and poly(ε-caprolactone) (PCL) was used as a three-dimensional (3D) culture for differentiation of hepatocyte-like cells and compared with routine culture (two-dimensional [2D]). The expression of the endodermal marker, forkhead box A2 (FOXA2), was assessed on Day 3 and the hepatic markers; albumin (ALB), α-1 antitrypsin (AAT), and cytokeratin-18 (CK-18) were evaluated on Day 18 using quantitative polymerase chain reaction qPCR...
December 4, 2018: Journal of Cellular Physiology
Zachary M Connelly, Shu Yang, Fenghua Chen, Yunshin Yeh, Nazih Khater, Renjie Jin, Robert Matusik, Xiuping Yu
Prostate cancer (PCa) is the leading cancer among men. Androgen Deprivation Therapy (ADT) is a common treatment for advanced PCa. However, ADT eventually fails and PCa relapses, developing into castration-resistant prostate cancer (CRPCa). Although alternative pathways such as cancer stem-cell pathway and neuroendocrine differentiation bypass androgen receptor (AR) signaling, AR remains the central player in mediating CRPCa. In this study, we identified a mechanism that retains AR signaling after androgen deprivation...
2018: American Journal of Clinical and Experimental Urology
Sara Ibrahim, Rania Dayoub, Sabrina Krautbauer, Gerhard Liebisch, Anja Kathrin Wege, Michael Melter, Thomas S Weiss
Cholestasis represents pathophysiologic syndromes defined as an impaired bile flow from the liver. As an outcome, bile acids accumulate and promote hepatocytes injury followed by liver cirrhosis and liver failure. Bile acids induce apoptosis, ER stress and mitochondrial membrane instability. In this study we aimed to investigate the role of cytosolic short form of ALR (Augmenter of Liver Regeneration) in the synthesis of bile acids and bile acid-induced apoptosis. Human hepatoma cells over-expressing the short form of ALR (sfALR, 15kDa) were incubated with glycochenodeoxycholic acid (GCDCA), and then primary bile acids' production and apoptosis were analyzed...
November 27, 2018: Experimental Cell Research
Jian Hou, Yan Long, Bo Hu, Shaojie Huang, Guangtao Xu, Tesheng Gao, Fenfang Wu, Yinxiong Li, Zhong-Kai Wu
BACKGROUND/AIMS: Hepatocyte-like cells derived from human pluripotent stem cells could be an important cell source for hepatocyte transplantation. The present study investigated the effect of retaining mTeSR1 medium during hepatic differentiation on hepatocyte-like cells in vitro. METHODS: Human embryonic stem cell line H1 were treated with activin A and bone morphogenetic protein 4 (BMP4) for definitive endoderm (DE) cell induction and subsequently treated with BMP2 and fibroblast growth factor 4 (FGF4) for early hepatic cell induction...
November 29, 2018: Cellular Physiology and Biochemistry
Soledad A Camolotto, Shrivatsav Pattabiraman, Timothy L Mosbruger, Alex Jones, Veronika K Belova, Grace Orstad, Mitchell Streiff, Lydia Salmond, Chris Stubben, Klaus H Kaestner, Eric Snyder
Changes in cancer cell identity can alter malignant potential and therapeutic response. Loss of the pulmonary lineage specifier NKX2-1 augments the growth of KRAS-driven lung adenocarcinoma and causes pulmonary to gastric transdifferentiation. Here we show that the transcription factors FoxA1 and FoxA2 are required for initiation of mucinous NKX2-1-negative lung adenocarcinomas in the mouse and for activation of their gastric differentiation program. Foxa1/2 deletion severely impairs tumor initiation and causes a proximal shift in cellular identity, yielding tumors expressing markers of the squamocolumnar junction of the gastrointestinal tract...
November 26, 2018: ELife
Irina Brokhman, Jie Xu, Brenda L K Coles, Rozita Razavi, Silvia Engert, Heiko Lickert, Robert Babona-Pilipos, Cindi M Morshead, Eric Sibley, Chin Chen, Derek van der Kooy
The enteric nervous system is thought to originate solely from the neural crest. Transgenic lineage tracing revealed a novel population of clonal pancreatic duodenal homeobox-1 (Pdx1)-Cre lineage progenitor cells in the tunica muscularis of the gut that produced pancreatic descendants as well as neurons upon differentiation in vitro. Additionally, an in vivo subpopulation of endoderm lineage enteric neurons, but not glial cells, was seen especially in the proximal gut. Analysis of early transgenic embryos revealed Pdx1-Cre progeny (as well as Sox-17-Cre and Foxa2-Cre progeny) migrating from the developing pancreas and duodenum at E11...
November 22, 2018: Developmental Biology
Pooja Chaudhari, Lipeng Tian, Amy Kim, Qingfeng Zhu, Robert Anders, Kathleen B Schwarz, Saul Sharkis, Zhaohui Ye, Yoon-Young Jang
Directed differentiation of human induced pluripotent stem cells (iPSCs) toward hepatobiliary lineages has been increasingly used as models of human liver development/diseases. As protein kinases are important components of signaling pathways regulating cell fate changes, we sought to define the key molecular mediators regulating human liver development using inhibitors targeting tyrosine kinases during hepatic differentiation of human iPSCs. A library of tyrosine kinase inhibitors was used for initial screening during the multi-stage differentiation of human iPSCs to hepatic lineage...
November 24, 2018: Stem Cells
Kangmu Ma, Xiaobei Deng, Xiaohuan Xia, Zhaohuan Fan, Xinrui Qi, Yongxiang Wang, Yuju Li, Yizhao Ma, Qiang Chen, Hui Peng, Jianqing Ding, Chunhong Li, Yunlong Huang, Changhai Tian, Jialin C Zheng
Background: Cell replacement therapy has been envisioned as a promising treatment for neurodegenerative diseases. Due to the ethical concerns of ESCs-derived neural progenitor cells (NPCs) and tumorigenic potential of iPSCs, reprogramming of somatic cells directly into multipotent NPCs has emerged as a preferred approach for cell transplantation. Methods: Mouse astrocytes were reprogrammed into NPCs by the overexpression of transcription factors (TFs) Foxg1, Sox2, and Brn2...
2018: Translational Neurodegeneration
J Zhang, S-L Hu, C-H Qiao, J-F Ye, M Li, H-M Ma, J-H Wang, S-Y Xin, Z-L Yuan
OBJECTIVE: Our study aimed to investigate the role of lncRNA-Neighboring Enhancer of FOXA2 (NEF) in esophageal squamous-cell carcinoma. PATIENTS AND METHODS: Tumor tissues and adjacent tissues were obtained from esophageal squamous-cell carcinoma patients, and blood samples were extracted from both patients with esophageal squamous-cell carcinoma and healthy volunteers. The expression of NEF was detected by quantitative Real-Time Polymerase Chain Reaction (qRT-PCR)...
October 2018: European Review for Medical and Pharmacological Sciences
Elham Hoveizi, Shima Tavakol
Diabetes mellitus is an autoimmune and chronic disorder that is rapidly expanding worldwide due to increasing obesity. In the current study, we were able to design a reliable 3-dimensional differentiation process of human Wharton's jelly mesenchymal stem cells into pancreatic beta cell precursors (PBCPs) and detected that transplanted PBCPs could improve hyperglycemia in a diabetes-induced model in mice. Polylactic acid/chitosan nanofibrous scaffold was prepared using an electrospinning method. Quantitative real-time reverse transcription-polymerase chain reaction and immunocytochemistry analysis were carried out to assess pancreatic marker expression in the differentiated cells...
November 1, 2018: Journal of Cellular Physiology
Shuyan Zhou, Furong Li, Yang Li, Cui Zhang, Yao Sun, Genbao Zhang
Objective To investigate a protocol for the efficient differentiation of human induced pluripotent stem cells (hiPSCs) into insulin-producing cells (IPCs) in vitro. Methods Lysine-specific demethylase 1 (LSD1) gene was knocked down in hiPSCs by RNAi. A four-step method was performed to induce the differentiation of hiPSCs into IPCs. The differentiation efficiency of IPCs was analyzed by flow cytometry. Real-time quantitative PCR was used to detect the mRNA levels of LSD1, OCT4, SOX17, FOXA2, PDX1, PAX4, PAX6, HNF6, TCF1, NKX6...
August 2018: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
Yaqing Wang, Hui Wang, Pengwei Deng, Wenwen Chen, Yaqiong Guo, Tingting Tao, Jianhua Qin
Liver organoids derived from human pluripotent stem cells (PSCs) represent a new type of in vitro liver model for understanding organ development, disease mechanism and drug testing. However, engineering liver organoids with favorable functions in a controlled cellular microenvironment remains challenging. In this work, we present a new strategy for engineering liver organoids derived from human induced PSCs (hiPSCs) in a 3D perfusable chip system by combining stem cell biology with microengineering technology...
December 7, 2018: Lab on a Chip
Xiaoqiu Wang, Xilong Li, Tianyuan Wang, San-Pin Wu, Jae-Wook Jeong, Tae Hoon Kim, Steven L Young, Bruce A Lessey, Rainer B Lanz, John P Lydon, Francesco J DeMayo
Mammalian pregnancy depends on the ability of the uterus to support embryo implantation. Previous studies reveal the Sox17 gene as a downstream target of the Pgr-Gata2-dependent transcription network that directs genomic actions in the uterine endometrium receptive for embryo implantation. Here, we report that ablating Sox17 in the uterine epithelium impairs leukemia inhibitory factor (LIF) and Indian hedgehog homolog (IHH) signaling, leading to failure of embryo implantation. In vivo deletion of the SOX17-binding region 19 kb upstream of the Ihh locus by CRISPR-Cas technology reduces Ihh expression specifically in the uterus and alters proper endometrial epithelial-stromal interactions, thereby impairing pregnancy...
October 24, 2018: Nature Communications
Qing-Miao Zhang, Wei-Xiang Ouyang, Xin-Qun Chai, Fei-Tao Deng
This study investigated the expression of lung surfactant proteins (SP-B and SP-C), and regulatory factors [forkhead box A2 (FOXA2) and nitrolyogenic FOXA2 (N-FOXA2)] in the fetal lung of rats with gestational diabetes mellitus (GDM) in order to study the mechanism of pulmonary dysplasia. The rat GDM model was established by using streptozotocin intraperitoneally in the first stage of pregnancy. There were 10 rats in the GDM group, and 10 healthy rats in normal control group without any treatment. Fetal lungs of two groups were taken at day 21 of pregnancy...
October 2018: Current medical science
Qingmiao Zhang, Xinqun Chai, Feitao Deng, Weixiang Ouyang, Ting Song
Hyperglycemia during pregnancy is associated with fetal lung development disorders and surfactant protein (SP) deficiency. Here, we examined the role of FOXA2 and Akt signaling in fetal lung development during diabetic pregnancy. Sprague-Dawley rats were injected with streptozocin (STZ) during pregnancy to induce diabetes (DM). DM-exposed fetal lungs exhibited reduced numbers of alveoli, irregularities in the appearance and thickness of the alveolar septum, increased levels of glycogen and lipids in type II alveolar epithelial cells, fewer microvilli and mature lamellar bodies, and swollen mitochondria...
October 2018: FEBS Open Bio
Wenze Niu, Tong Zang, Lei-Lei Wang, Yuhua Zou, Chun-Li Zhang
Neuronal subtype is largely fixed in the adult mammalian brain. Here, however, we unexpectedly reveal that adult mouse striatal neurons can be reprogrammed into dopaminergic neuron-like cells (iDALs). This in vivo phenotypic reprogramming can be promoted by a stem cell factor (SOX2), three dopaminergic neuron-enriched transcription regulators (NURR1, LMX1A, and FOXA2), and a chemical compound (valproic acid). Although the site of action of the reprogramming factors remains to be determined, immunohistochemistry and genetic lineage mappings confirm striatal neurons as the cell origin for iDALs...
November 13, 2018: Stem Cell Reports
Nitya V Sharma, Kathryn L Pellegrini, Veronique Ouellet, Felipe O Giuste, Selvi Ramalingam, Kenneth Watanabe, Eloise Adam-Granger, Lucresse Fossouo, Sungyong You, Michael R Freeman, Paula Vertino, Karen Conneely, Adeboye O Osunkoya, Dominique Trudel, Anne-Marie Mes-Masson, John A Petros, Fred Saad, Carlos S Moreno
BACKGROUND: Patients with locally advanced or recurrent prostate cancer typically undergo androgen deprivation therapy (ADT), but the benefits are often short-lived and the responses variable. ADT failure results in castration-resistant prostate cancer (CRPC), which inevitably leads to metastasis. We hypothesized that differences in tumor transcriptional programs may reflect differential responses to ADT and subsequent metastasis. RESULTS: We performed whole transcriptome analysis of 20 patient-matched Pre-ADT biopsies and 20 Post-ADT prostatectomy specimens, and identified two subgroups of patients (high impact and low impact groups) that exhibited distinct transcriptional changes in response to ADT...
October 11, 2018: Cancers
Lei Ye, Lei X Sun, Min H Wu, Jin Wang, Xin Ding, Hui Shi, Sheng L Lu, Lin Wu, Juan Wei, Liang Li, Yu F Wang
Disruption of normal barrier function is a fundamental factor in the pathogenesis of inflammatory bowel disease, and intestinal stem cell (ISC) transplantation may be an optional treatment for patients. However, it is complicated and inefficient to isolate ISCs from the intestine, which hampers its wide application in clinic. We developed a two-step protocol in which mesenchymal stem cells (MSCs) were first induced into Sox17- or Foxa2-positive definitive endoderm cells by activin A treatment and then into Lgr5-positive ISC-like cells by miR-17 and FGF2 treatment...
August 24, 2018: Molecular Therapy. Nucleic Acids
Simmi Saini, Gagandeep Kaur Walia, Mohinder Pal Sachdeva, Vipin Gupta
Obesity is one of the largest global health problems associated with increased morbidity and mortality mediated by its association with several other metabolic disorders. The interaction between the genes and environment plays an important role in the manifestation of obesity. Despite a high heritability (40-70%) of obesity, the search for genetic variants associated with obesity susceptibility has been a challenging task. To date, limited studies have been conducted in India, restricted to the validation of few genetic variants identified by genomewide association studies...
September 2018: Journal of Genetics
Nishanth Uli, Eduardo Michelen-Gomez, Enrique I Ramos, Todd E Druley
The role of DNA methylation patterns in complex phenotypes remains unclear. To explore this question, we adapted our methods for rare variant analysis to characterize genome-wide murine DNA hybridization array to investigate methylation at CpG islands, shores, and regulatory elements. We have applied this platform to compare age and tissue- specific methylation differences in the brain and spleen of young and aged mice. As expected from prior studies, there are clear global differences in organ-specific, but not age-specific, methylation due mostly to changes at repetitive elements...
2018: PloS One
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