Bar-Ilan University

About: Bar-Ilan University is a education organization based out in Ramat Gan, Israel. It is known for research contribution in the topics: Population & Poison control. The organization has 12835 authors who have published 34964 publications receiving 995648 citations. The organization is also known as: Bar Ilan University & BIU.

DNA methylation analysis of the autistic brain reveals multiple dysregulated biological pathways

Abstract: Autism spectrum disorders (ASD) are a group of neurodevelopmental conditions characterized by dysfunction in social interaction, communication and stereotypic behavior. Genetic and environmental factors have been implicated in the development of ASD, but the molecular mechanisms underlying their interaction are not clear. Epigenetic modifications have been suggested as molecular mechanism that can mediate the interaction between the environment and the genome to produce adaptive or maladaptive behaviors. Here, using the Illumina 450 K methylation array we have determined the existence of many dysregulated CpGs in two cortical regions, Brodmann area 10 (BA10) and Brodmann area 24 (BA24), of individuals who had ASD. In BA10 we found a very significant enrichment for genomic areas responsible for immune functions among the hypomethylated CpGs, whereas genes related to synaptic membrane were enriched among hypermethylated CpGs. By comparing our methylome data with previously published transcriptome data, and by performing real-time PCR on selected genes that were dysregulated in our study, we show that hypomethylated genes are often overexpressed, and that there is an inverse correlation between gene expression and DNA methylation within the individuals. Among these genes there were C1Q, C3, ITGB2 (C3R), TNF-α, IRF8 and SPI1, which have recently been implicated in synaptic pruning and microglial cell specification. Finally, we determined the epigenetic dysregulation of the gene HDAC4, and we confirm that the locus encompassing C11orf21/TSPAN32 has multiple hypomethylated CpGs in the autistic brain, as previously demonstrated. Our data suggest a possible role for epigenetic processes in the etiology of ASD.

Mesenchymal stem cells deliver synthetic microRNA mimics to glioma cells and glioma stem cells and inhibit their cell migration and self-renewal.

Abstract: // Hae Kyung Lee 1 , Susan Finniss 1 , Simona Cazacu 1 , Efrat Bucris 2 , Amotz Ziv-Av 2 , Cunli Xiang 1 , Kevin Bobbitt 3 , Sandra A. Rempel 4 , Laura Hasselbach 5 , Tom Mikkelsen 5 Shimon Slavin 6 and Chaya Brodie 1,2 1 Davidson Laboratory of Cell Signaling and Tumorigenesis, Hermelin Brain Tumor Center, Department of Neurosurgery, Henry Ford Hospital, Detroit, MI, 2 Everard and Mina Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, Israel, 3 Department of Public Health Sciences, 4 Barbara Jane Levy Laboratory of Molecular Neuro-Oncology, 5 Eugene & Marcia Applebaum Laboratory of Invasion & Molecular Therapeutics and 6 The international center for Cell Therapy and Cancer Immunotherapy (CTCI), Tel Aviv, Israel Correspondence: Chaya Brodie, email: // Keywords : miRNA delivery, mesenchymal stem cells, glioma, exosomes Received : February 12, 2013 Accepted : February 27, 2013 Published : February 28, 2013 Abstract MicroRNAs (miRNAs) have emerged as potential cancer therapeutics; however, their clinical use is hindered by lack of effective delivery mechanisms to tumor sites. Mesenchymal stem cells (MSCs) have been shown to migrate to experimental glioma and to exert anti-tumor effects by delivering cytotoxic compounds. Here, we examined the ability of MSCs derived from bone marrow, adipose tissue, placenta and umbilical cord to deliver synthetic miRNA mimics to glioma cells and glioma stem cells (GSCs). We examined the delivery of miR-124 and miR-145 mimics as glioma cells and GSCs express very low levels of these miRNAs. Using fluorescently labeled miRNA mimics and in situ hybridization, we demonstrated that all the MSCs examined delivered miR-124 and miR-145 mimics to co-cultured glioma cells and GSCs via gap junction–dependent and independent processes. The delivered miR-124 and miR-145 mimics significantly decreased the luciferase activity of their respected reporter target genes, SCP-1 and Sox2, and decreased the migration of glioma cells and the self-renewal of GSCs. Moreover, MSCs delivered Cy3-miR-124 mimic to glioma xenografts when administered intracranially. These results suggest that MSCs can deliver synthetic exogenous miRNA mimics to glioma cells and GSCs and may provide an efficient route of therapeutic miRNA delivery in vivo .