PADIS

Pubblicazioni Aperte DIgitali Sapienza > MEDICINA SPERIMENTALE > MEDICINA MOLECOLARE >

Please use this identifier to cite or link to this item: http://hdl.handle.net/10805/1998

Title: Interplay of Nanog and microRNAs in controlling stemness and proliferation in Neural Stem Cells
Authors: GARG, NEHA
Tutor: GULINO, ALBERTO
FERRETTI, ELISABETTA
Keywords: NANOG
MICRORNA
HEDGEHOG
STEM CELLS
Issue Date: 22-Feb-2013
Abstract: The maintenance of Neural Stem Cells (NSC) from different niches of embryonic or postnatal forebrain (subventricular zone and hippocampus) as well as cerebellum is promoted by a number of stemness genes (e.g. Nanog, Oct4, Sox2). Inspite of our good understanding of the mechanisms regulating these stemness drivers, there is a poor knowledge about their target genes, whereby stem cell features are regulated. We identify herein miR-17/92 cluster as a target of Nanog. Nanog controls miR-17/92 cluster by binding to the upstream regulatory region and enhancing its transcription in NSC. Whereas miR-17/92 expression is upregulated in NSC, it decreases alongside differentiation and cell maturation. MiR-17 family further enhances both clonogenicity and proliferation of NSC. Conversely, antagonizing miR-17 family yields an opposing effect. MiR-17 family has a number of potential targets involved in cell cycle and proliferation. We identify here the Transformation related protein 53-induced nuclear protein 1 (TRP53INP1), a proapoptotic stress-induced p53 target gene. MiR-17 family expression paralleled the reduced TRP53INP1 levels. Silencing TRP53INP1 in NSC enhances both self-renewal and proliferation. Infact the increase of Nanog and miR-17 family expression helps in transition from G1 to S phase of NSC cycle coinciding with the reduction of TRP53INP1. Collectively, Nanog via miR-17/92 cluster regulates NSC by silencing TRP53INP1. These findings allowed us to expand the regulatory circuitry of p53 signalling via Nanog in NSC and suggested the role of miRNAs in the maintenance of NSC.
URI: http://hdl.handle.net/10805/1998
Research interests: Stem cells, Hedgehog signaling, Nanog, microRNAs, proteomics, leukemia, high-throughput analysis.
Personal skills keywords: Neural Stem cells
microRNAs expression and analysis
high-throughput analysis.
proteomics
Hedgehog signaling
Appears in PhD:MEDICINA MOLECOLARE

Files in This Item:

File Description SizeFormat
GARG NEHA_PHD THESIS 22FEB 2013.pdfPHD THESIS, GARG NEHA10.01 MBAdobe PDF

File del Curriculum Vitae:

CurriculumVitae.pdf 117.83 kBAdobe PDF


This item is protected by original copyright

Recommend this item

Items in PADIS are protected by copyright, with all rights reserved, unless otherwise indicated.

 

Valid XHTML 1.0! DSpace Software Copyright © 2002-2010  Duraspace - Feedback Sviluppo e manutenzione a cura del CINECA