G Marazzi & D Sassoon
Dr V. Besson, a postdoctoral researcher in the team co-led by G. Marazzi and D. Sassoon (UMR 787 - Myology Group) has generated murine reporter line allowing to easily identify stem cells in adult tissues.
What makes this mouse model simple?
We chose an easily identifiable marker, beta-galactosidase, which stains cells blue in the presence of X-gal, to monitor the PW1 protein. A few years ago we isolated this protein as being a marker of muscle stem cells (SC): satellite cells and interstitial cells (PICs). So when PW1 is expressed in the muscle, it is blue.
Is this what you observed?
When verifying the validity of the model, it was found that PW1 marked not only the SC of the muscle, but also SCs of other tissues (intestine, brain, blood or skin) as well as Scs of tissues where SCs are less well-known or not known at all. In addition, the SCs thus marked are competent (not only capable of differentiating into various cell types but also able to self-renew many times).
In addition, the intensity of blue depends on the nature of the SC. It is very intense when the cell is the progenitor and paler in the presence of stem cells with more limited capacity. The labelling thus gives us a quantitative indication of the differentiation capacity of SC.
Can this model serve as a tool to develop therapeutic approaches?
Absolutely, it is precisely the competence of the SC that is interesting for therapy. The advantage of this model is that it can be purified on the basis of the intensity of blue and their competence studied in vitro. More broadly, this model can be used to quickly identify new molecules and drugs targeted for degenerative diseases. It also allows to directly test drugs under development to monitor their effects on SC in vivo.
What are the next steps?
We will analyse the SC to understand them better and discover the mechanisms that regulate them, the conditions under which they can be amplified and therefore identify the growth factors, or how to mobilise them in a coordinated fashion. In parallel, we have established collaborations with other laboratories to work on heart, pancreas and spinal cord SCs. And we will continue to work on muscle SCs and their characteristics.
What makes this mouse model simple?
We chose an easily identifiable marker, beta-galactosidase, which stains cells blue in the presence of X-gal, to monitor the PW1 protein. A few years ago we isolated this protein as being a marker of muscle stem cells (SC): satellite cells and interstitial cells (PICs). So when PW1 is expressed in the muscle, it is blue.
Is this what you observed?
When verifying the validity of the model, it was found that PW1 marked not only the SC of the muscle, but also SCs of other tissues (intestine, brain, blood or skin) as well as Scs of tissues where SCs are less well-known or not known at all. In addition, the SCs thus marked are competent (not only capable of differentiating into various cell types but also able to self-renew many times).
In addition, the intensity of blue depends on the nature of the SC. It is very intense when the cell is the progenitor and paler in the presence of stem cells with more limited capacity. The labelling thus gives us a quantitative indication of the differentiation capacity of SC.
Can this model serve as a tool to develop therapeutic approaches?
Absolutely, it is precisely the competence of the SC that is interesting for therapy. The advantage of this model is that it can be purified on the basis of the intensity of blue and their competence studied in vitro. More broadly, this model can be used to quickly identify new molecules and drugs targeted for degenerative diseases. It also allows to directly test drugs under development to monitor their effects on SC in vivo.
What are the next steps?
We will analyse the SC to understand them better and discover the mechanisms that regulate them, the conditions under which they can be amplified and therefore identify the growth factors, or how to mobilise them in a coordinated fashion. In parallel, we have established collaborations with other laboratories to work on heart, pancreas and spinal cord SCs. And we will continue to work on muscle SCs and their characteristics.
PW1 gene/paternally expressed gene 3 (PW1/Peg3) identifies multiple adult stem and progenitor cell populations.
Besson V, Smeriglio P, Wegener A, Relaix F, Nait Oumesmar B, Sassoon DA, Marazzi G.
Proc Natl Acad Sci U S A. 2011 Jul 12;108(28):11470-5. Epub 2011 Jun 27.
Besson V, Smeriglio P, Wegener A, Relaix F, Nait Oumesmar B, Sassoon DA, Marazzi G.
Proc Natl Acad Sci U S A. 2011 Jul 12;108(28):11470-5. Epub 2011 Jun 27.
September 2011
Interview of G. Marazzi & D. Sassoon by Anne Berthomier, translation by Racquel N. Cooper
Interview of G. Marazzi & D. Sassoon by Anne Berthomier, translation by Racquel N. Cooper
