“Pluripotent stem cells: capture of the ground state”. Austin Smith

Austin Smith is probably the investigator that is constantly giving more indications on how to capture the ground state of pluripotent stem cells. His work is based on the characterization of the ground state of pluripotent stem cell lines cultured with different conditions. Embryonic stem cells (ESCs) could be cultured in vitro as an homogenous population. Despite they are used as a general model of pluripotent cells, it has to be take into account that their gene expression profile match with a specific subset of cells that, during the embryonic development in vivo, is present in a specific space and time. Austin Smith define a new culture condition of human ESCs through which it is possible to capture a ground state quite similar to the once of human embryo tissues and to mouse ES cell lines but different from the current human ES cell lines characterized.

“Cancer drivers and Dependencies”. Scott Lowe

The path of cancer evolution dictates the tumor response to therapy and creates unique vulnerabilities that represent therapeutic opportunities. Based on this concept, Lowe’s Lab is developing powerful methods to follow the behavior of tumor-initiating cells in normal tissues in living mice. Moreover, using inducible RNA interference systems, they suppressed the function of different genes in vivo in a stable and reversible manner in order to characterize cancer drivers and the dependencies they create. Fascinating results were shown on the reversibility of gastrointestinal malignancies phenotypes turning on and off the function of specific factors.

“Long-range regulation during development and evolution”. Denis Duboule

The formation of digits during development is a high regulated process coordinates by the Hoxd genes. By analyzing the chromosome conformation and Hox transcriptional regulation during the process, Duboule’s Lab showed that the active part of the Hoxd gene cluster contacts with several regulatory islands within the centromere. Interestingly, a similar regulatory organization was found during the development of external genitals. Moreover, a similar situation is observed at the HoxA locus. Denis Duboule discussed about potential common mechanisms for Hox genes transcriptional regulation in different contexts.

“Mature hepatocytes are source of bipotential oval cells in chronic liver injury”. Markus Grompe

The liver is an organ with a high regeneration potential and Markus Grompe is one of the most excellent scientists working in this field. Using lineage tracing mice, he tracked hepatic stem cells that are suppose to product oval cells during severe liver injury. Surprisingly, no oval cells derived from the differentiation of hepatic stem cells were found in presence of different liver injuries. On the other side, mature hepatocytes seem to undergo a reprogramming process forming hepatocyte-derived progenitors that in turn can differentiate to become fully functional hepatocytes. This results suggest that a reprogramming process of mature hepatocytes, and not the classical differentiation of the existing hepatic stem cells, mediates the regenerative response to liver injury providing new fascinating insights into the mechanisms of tissue regeneration.

“Mechanisms for programming cell fate”. Kenneth Zaret

The concept that it is possible to reprogram the cell fate for therapeutic purpose is one of the hottest field of the last years. Kenneth Zaret is investigating the mechanisms that regulate changes in gene expression during reprogramming. Starting from the evidence that transcription factors “pioneer” in the activation of a reprogramming process could invade silent chromatin, he focused his attention on the affinity of these factors for specific DNA conformations. Interestingly, all the pioneer factors seems to have a high capability to adapt to the nucleosomes for which they show high affinity. Thus, studying the protein conformation it could be possible to identify other possible pioneer factors that could be tested for their role in the mediation of a reprogramming process.