Cellular Biotechnology

Control of stem cell potency

Prof. Dr. Raya, Ángel
(ICREA Research Professor)
Group Leader


Ed. Hèlix | Baldiri Reixac, 15-21 | 08028 | Barcelona
Email : arayaibecbarcelona.eu

Research Topics

Heart regeneration in the zebrafish / Mechanisms of induced reprogramming to pluripotency / Disease modeling through induced pluripotent stem (iPS) cells / Induced reprogramming to cardiogenic mesoderm / Bioengineering approach to heart muscle differentiation

 

During embryo development, the potency of the zygote is deployed through coordinated and stereotypical changes in cell behaviors and tissue patterning processes, ultimately resulting in the formation of an entire, highly complex organism in a relatively short period of time. With two remarkable exceptions, this process is irreversible—that is, the progressive increase in the complexity of the system is coupled to a decrease in the overall potency of its constituents. One such exception is regeneration, a phenomenon by which the cells of certain organisms re-acquire potency and the capacity to rebuild lost parts or structures. Developmental potency can also be regained experimentally through a process called reprogramming, either by nuclear transfer, cell fusion with pluripotent cells, or, more recently, induced reprogramming by defined factors.

 

Brightfield images of a zebrafish heart before (left) and after (right) decellularization. Decellularized hearts provide useful matrices to investigate extracellular cues underlying regeneration.


 

 

 

 

Using a multipronged approach, our laboratory takes advantage of recent conceptual and technical developments to address the basic question of how a discrete and defined degree of developmental potency can be imposed on a somatic cell, thereby enabling it to regain the capacity to regenerate a functional tissue or structure.
For this purpose, we mainly use the paradigm of heart (re)generation.

Overall, our research is based on the following working hypotheses:

1) Careful investigation of the mechanisms that control zebrafish heart regeneration will uncover the critical transcriptional and epigenetic features that underlie the re-acquisition of developmental potency;

2) By using a combination of specific factors and appropriate selection procedures we will be able to partially reprogram somatic cells to create multipotent cardiogenic progenitors;

3) Providing adequate extracellular cues to suitable pluripotent or multipotent progenitors will guide their intrinsic potential to generate functional myocardial tissue.

 

Muscle cells differentiated in vitro from human
iPS cells, stained for specific markers.