The Institute of Stem Cell Research investigates the basic molecular and cellular mechanisms for stem cell maintenance and stem cell differentiation. The research focus encompasses basic mechanisms regulating stem cell self-renewal using several sets of embryonic and adult stem cells in an interactive and comparative manner. A further focus of research in this institute is also the identification of differentiation mechanisms that enable the replacement of certain cell types in disease models by eliciting this program from endogenous stem cells or re-programming other endogenous cells for repair.
Neural Stem Cells Group (M. Götz):
The aim of this working group is to understand the mechanisms underlying neurogenesis sufficiently well to elicit these mechanisms also in the adult brain, where repair of degenerated neurons from endogenous sources has not yet been achieved. Using global gene expression analysis we could not only unravel the molecular mechanisms of disctinct modes of neurogenesis from glial cells during development, but also how to instruct glial cells in the injured brain towards the generation of new neurons. Moreover, by understanding the transcriptional program of neuronal fate determinants, we succeeded to efficiently reprogram mature glial cells towards fully functional neurons. Our work on mechanisms of adult neurogenesis also allowed to discover a new source of progenitor cells for glutamatergic neurons in the adult mose brain which can also be utilized for repair as these cells migrate after damage into the cerebral cortex and regenerate new glutamatergic projection neurons.
More about Neural Stem Cells
Endodermal Stem Cells Group (H. Lickert):
This previously funded Emmy-Noether research group focuses primarily on development and regeneration of the lung and pancreas. Both, embryonic stem (ES) cell differentiation and mouse developmental studies are used to identify the progenitor cells and the respective signals, which lead to cell differentiation and organ formation. Live imaging of ES cells, mouse embryos and organ cultures are used to understand development and differentiation on a cell biological level. Various screenings have led to the identification of novel developmental genes implicated in organ formation and homeostasis. Moreover, the function of cilia in cellular communication and organogenesis of endodermal organs are also being investigated (European Re¬search Council Starting Grant, €1.5 mil for innovative research).
Mammary Stem Cells (C. Scheel)
The focus of the Scheel research group is on the molecular control of stem cell traits in normal breast epithelial cells and in breast cancer cells. We are especially interested in the role of growth factors and morphogens in normal and malignant human breast epithelial stem cells and in elucidating the signal transduction pathways that are activated by them. To achieve this, we use state-of-the-art innovative methodologies for the isolation, manipulation and culture of human adult stem cells. One important insight that we and others have gained recently is that stem cell programs of normal tissue homeostasis and tumor progression have many similarities on the molecular level. That is why, on the one hand, we are interested in the controlled induction of stem cell traits in normal breast epithelial cells in order to develop protocols for the derivation of a large number of adult epithelial stem cells for applications in regenerative medicine. On the other hand, we are seeking to develop therapeutic strategies to inhibit signal transduction pathways that induce and maintain stem cell traits in tumors. Here we are cooperating closely with our clinical partners at the Institute of Pathology of the Ludwig-Maximilians-Universität in Munich. We are supported by the Max Eder Young Investigator Start-up Grant of the German Cancer Aid.
Human Pluripotent Stem Cells (M. Drukker)
The research aim of the group is to investigate the molecular program governing commitment of human pluripotent stem cells to embryonic progenitors that give rise to fetal organs. Human embryonic stem cells (ESCs) can differentiate into the dazzling array of cell types which make us what we are. That’s way human ESCs have the potential to revolutionize medicine by supplying cells and tissues for regenerative therapies. Although “Differentiation” is regularly used as a term to describe the phenotypic changes that ESCs undergo while acquiring specialized functions, the sequences of cell fate choices leading to “committed” cells are not well characterized. In fact, even the lineage-committed progenitors that emerge directly from pluripotent cells and the underlying patterns of fate choices remain uncharacterized.
Until very recently, it was difficult to analyze distinct lineages in differentiating cultures since human ESCs produce mixtures of embryonic-like cell types. This situation has recently improved by our identification of cell surface markers that are specifically expressed by few of earliest developmental progenitors that emerge from human ESCs (Drukker et at Nature Biotechnology 2012). These surface markers provide us a platform to purify progenitors through cell sorting and to monitor their development utilizing advanced time-lapse microscopy methods.