Pluripotency and reprograming
Initiators: Micha Drukker (Munich), Mathias Treier (Berlin) and Hans Schöler (Munster)
Pluripotent stem cells (PSCs) are unique in their capacity to self-renew indefinitely in culture while retaining the potential to give rise to all cell types of the body. PSCs are maintained at the naïve state through the concerted action of a network of transcription factors promoting cell division and assembly of chromatin architecture. However, these factors also regulate and enable activation of commitment programs. Forced expression of only a handful of factors, including the key pluripotency factors Oct4 and Sox2 and/or small molecules promotes reprograming of somatic and germ cells to the pluripotent state enabling establishment of cell lines (termed induced pluripotent stem cells - iPSCs) that resemble embryonic stem cells (ESCs). Today somatic cells can also be transdifferentiated to cell types of other lineages by the expression of factors that control these lineages without going through a pluripotent state, i.e. the cells are directly reprogramed. Differentiation is a process (not a cell stage) where cells at the end are committed to a specialized task having lost their ability to easily become another cell type compared with the initial pluripotent stage. In the context of PSCs it refers to the restriction of developmental potential when cells commit to certain developmental branches. Every differentiation event involves the coordinated activation of numerous molecular cascades that are layed down as blueprint in our genome and the epigenome of PSCs, and are executed upon command (signals). These differentiation programs produce the dazzling array of cell types that are the prerequisite to make a multicellular organism like we are.
A list of key research topics in this work group include:
- Mechanisms regulating the pluripotent state, in particular naïve and primed ESCs
- Mechanisms regulating exist from pluripotency and commitment of embryonic progenitors
- The identification of developmental progenitors and characterization of their progenies
- Mechanisms governing reprograming and transdifferentiation, including epigenetic factors and signaling cascades
- Applications of PSCs for disease modeling and drug screening purposes, and regenerative treatments
An important mission of the “Pluripotency and Re-Programming” working group is to promote these research topics, and to pursuit fundamental questions and applied goals including (but not limited to):
- How similar are the specialized cells emerging during PSC differentiation to somatic cells?
- What is the equivalent stage of development of specialized cells that are derived from PSC? Do they resemble fetal, young or adult somatic cells, and how can we manipulate them to reach the desired stage?
- How do cells weight conflicting inputs instructing alternative lineage choice?
- How can we manipulate maintenance, expansion, and differentiation of developmental tissue progenitors that emerge from PSCs?
The working group has been formed to facilitate communications and collaborations between scientists working on PSCs and their derivatives and to bridge the gap between scientists conducting basic and applied studies. Another key mission is to identify key areas that the members of the GSCN would like to strengthen, and to act upon these requests by providing research tools, training tutorials and lobby for funding.