Battista, Marica
(2014)
miRNAs in the regulation of embryonic stem cell differentiation.
[Tesi di dottorato]
| Tipologia del documento: |
Tesi di dottorato
|
| Lingua: |
English |
| Titolo: |
miRNAs in the regulation of embryonic stem cell differentiation |
| Autori: |
| Autore | Email |
|---|
| Battista, Marica | maricabattista@gmail.com |
|
| Data: |
28 Gennaio 2014 |
| Numero di pagine: |
98 |
| Istituzione: |
Università degli Studi di Napoli Federico II |
| Istituzioni (extra): |
CEINGE Biotecnologie Avanzate |
| Scuola di dottorato: |
SEMM – European School of Molecular Medicine |
| Dottorato: |
PhD in Molecular Medicine (Molecular Oncology or Human Genetics) |
| Ciclo di dottorato: |
25 |
| Coordinatore del Corso di dottorato: |
| nome | email |
|---|
| Salvatore, Francesco | salvator@unina.it |
|
| Tutor: |
| nome | email |
|---|
| Russo, Tommaso | tommaso.russo@unina.it | | Pastore, Lucio | lucio.pastore@unina.it | | De Renzis, Stefano | stefano.derenzis@embl.de |
|
| Data: |
28 Gennaio 2014 |
| Numero di pagine: |
98 |
| Parole chiave: |
miRNA,ESC,TGF-beta |
| Settori scientifico-disciplinari del MIUR: |
Area 05 - Scienze biologiche > BIO/11 - Biologia molecolare |
| Aree tematiche (7° programma Quadro): |
SALUTE e TUTELA DEL CONSUMATORE > Biotecnologie, strumenti e tecnologie generiche per la salute umana |
[error in script]
[error in script]
| Informazioni aggiuntive: |
Ciclo VII/XXV, Curriculum Molecular Oncology |
| Depositato il: |
11 Feb 2014 15:47 |
| Ultima modifica: |
12 Gen 2015 14:05 |
| URI: |
http://www.fedoa.unina.it/id/eprint/9573 |
Abstract
Embryonic Stem cells (ESCs) have the unique characteristics of self-renew and differentiate into all the cells derived from the three germ layers. These properties make them a limitless source of specialized cells for replacement therapies. However, the knowledge of the mechanisms controlling ESC differentiation into lineage-specific derivatives is necessary before using them for therapeutic purposes. Extracellular signalling, as that of bone morphogenetic protein 4 (BMP4), plays an important role in maintaining ESCs in undifferentiated state and in regulating the lineage commitment. Recently, it was identified a transmembrane protein, named Dies1, which suppression blocks ESC differentiation by interfering with the BMP4 signalling. Over the past few years, it has become evident the involvement of miRNAs in the ESC fate. Thus, we investigated whether a physiological modulation of Dies1 level by miRNAs could be a mechanism regulating ESC choice between pluripotency and differentiation. We demonstrated that miR-125a and miR-125b control Dies1 expression targeting its 3’ UTR. Their overexpression impairs ESC differentiation, maintaining the cells in the epiblast state. This effect is due to a reduction of BMP4 signalling and a concomitant increase of Nodal/Activin pathway. This phenotype recapitulates that of Dies1 KD ESCs and is mediated by Dies1 suppression. Moreover we found that Dies1 is associated with BMP4 receptor complex and that BMP4 itself induces the expression of miR-125a at transcriptional level. This miRNA, in turn, controls BMP4 activity through Dies1 regulation. These results show that a feedback loop exists to set ESC sensitivity to BMP4, and it is mediated by miR-125a and Dies1. Interestingly, we found that miR-125b, opposite to miR-125a, is not directly regulated by Transforming Growth Factor-β (TGF-β) signals. These results demonstrate a new role of miR-125a and miR-125b in the regulation of the transition of ESCs to the epiblast stage, working on the control of TGFβ signalling.
Downloads per month over past year
Actions (login required)
 |
Modifica documento |
