Identification of genes that regulate bone marrow stromal cell differentiation by RNA interference

Cantilena, Bruno (2010) Identification of genes that regulate bone marrow stromal cell differentiation by RNA interference. [Tesi di dottorato] (Inedito)

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Abstract

Mesenchymal stem cells (MSCs) can be isolated from bone marrow and can differentiate in a variety of cell types, including osteoblasts, adipocytes, chondrocytes, myoblasts, hepatocytes, and neural cells. For this reason, MSCs are very promising for the development of cell-based therapy for degenerative diseases. Understanding the mechanisms behind MSC cell fate determination is not easy, since the molecular processes that drive differentiation are complex and poorly understood. Even though in the recent years many improvements have been done, many mechanism need to be elucidated. We planned to investigate on differentiation mechanisms of MSC and, in particular, we focused our activities towards osteoblast differentiation; at this aim, we have silenced specific mRNAs using a mouse shRNA library in a 96 well plate-based screening strategy. With this methodology we identified sevral genes that are possible candidates for a role in osteoblast differentiation. Among the candidate genes, a consistent fraction was represented by genes whose function is still unknown: we focused our attention on a short number of these genes that we named ObI (Osteoblast inducer). In this thesis project we focused our experiments on a particular gene, that we named ObI-1. We also considered genes identified during the screening with a known function but an unknown role during the osteogenic differentiation process. Among these genes we focused our attention on Angiotensin receptor 1 (AT1R), whose role in osteogenic differentiation had been previously suggested. For both candidates that we analyzed for this project we confirmed the effects of silencing on osteogenic differentiation and we analyzed expression in tissues and in our cell culture system. Furthermore, we characterized function and mechanism of action in osteoblastogenesis for both genes.

Tipologia di documento:Tesi di dottorato
Altre informazioni:Curriculum: Human Genetics
Parole chiave:Bone, osteoblast, mesenchymal stem cells, rna interference, differentiation
Settori scientifico-disciplinari MIUR:Area 05 Scienze biologiche > BIO/11 BIOLOGIA MOLECOLARE
Area 05 Scienze biologiche > BIO/13 BIOLOGIA APPLICATA
Coordinatori della Scuola di dottorato:
Coordinatore del Corso di dottoratoe-mail (se nota)
Salvatore, Francescosalvator@unina.it
Tutor della Scuola di dottorato:
Tutor del Corso di dottoratoe-mail (se nota)
Ramirez, Francescofrancesco.ramirez@gmail.com
Pastore, Luciopastore@ceinge.unina.it
Karsenty, Gerard
Stato del full text:Accessibile
Data:30 Gennaio 2010
Numero di pagine:124
Istituzione:Università degli studi di Napoli Federico II
Dipartimento o Struttura:CE.IN.GE. Bitecnologie Avanzate di Napoli
Tipo di tesi:Dottorato
Stato dell'Eprint:Inedito
Scuola di dottorato:SEMM - European School of Molecular Medicine) - sede di Napoli
Denominazione del dottorato:PhD in Molecular Medicine (Molecular Oncology or Human Genetics)
Ciclo di dottorato:XXI
Numero di sistema:4318
Depositato il:05 Febbraio 2010 17:16
Ultima modifica:13 Luglio 2012 11:36

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