Regulation and Role of Sox9 expression during hepatogenic differentiation

Dissertant

al-Malmi, Imani

Thesis advisor

Sindidi, Khalid Sadaqa
Nujaymi, Mustafa

Comitee Members

al-Asli, Abd al-Ghani
Barradah, Fuad

University

Al Akhawayn University

Faculty

School of Science and Engineering

Department

Biotechnology

University Country

Morocco

Degree

Master

Degree Date

2011

English Abstract

Sox9 is a transcription factor belonging to a specific sub-family of proteins.

The genes encoding for these proteins are characterized by a homologous sequence called HMG box (High Mobility Group box).

Sox9 is involved in several development mechanisms such as sex determination and chondrogenesis.

Recently, many evidences support its involvement in liver development.

Indeed, sox9 expression has been detected in liver progenitor cells and during biliary differentiation.

In this study, we attempted to investigate the role of Sox9 in hepatogenic differentiation.

The study was performed in vitro on well-established cell models of intra-hepatic and extra-hepatic origin.

Stem/progenitor cells isolated from healthy adult human liver as well as Wharton jelly have been particularly studied.

Besides analysis of Sox9 basal expression, RT-qPCR and immunocytochemistry have been used to evaluate the Sox9 expression profile after in vitro hepatogenic differentiation (according to a well standardized protocol).

Our data demonstrate that the studied stem/progenitor cells are constitutively expressing Sox9 in expansion culture conditions.

After in vitro hepatogenic differentiation, Sox9 expression significantly decreases which is in correlation with the low level observed in isolated mature human hepatocytes.

Furthermore, we demonstrate that the expression kinetics of Sox9 during the different steps of the hepatogenic differentiation protocol differ from cells of intra and extra-hepatic origin.

To demonstrate the involvement (or not) of Sox9 in controlling hepatogenic differentiation of stem/progenitor cells, a double strategy has been used in the second part of the study.

Firstly, activators and inhibitors of Sox9 expression have been supplemented during the in vitro hepatogenic differentiation.

Secondly, Sox9 expression has been stably silenced using shRNA approach.

The impact of the modulation of Sox9 expression using these two strategies has been evaluated on the quality of hepatogenic differentiation of liver stem/progenitor cells.

The study presented here has initially been designed to understand and decode the Sox9 related mechanisms that may trigger hepatogenic differentiation of mesenchymal stem/progenitor cells.

The appreciation of such mechanisms would be useful for twigging post-natal liver regeneration and development of stem/progenitor cell-based therapies.

Main Subjects

Biology

Topics

• Molecular genetics

No. of Pages

62

Table of Contents

• APA
• MLA
• AMA

Language

English

Data Type

Arab Theses

Record ID

BIM-645024