Bioinformatics for Stem Cell Research

In collaboration with the University of Cambridge, scientists of the Institute of Computational Biology have identified important differentiation pathways of stem cells by means of expression patterns of transcription factors. 

Scientists of the Institute of Computational Biology at Helmholtz Zentrum München, together with colleagues from the Stem Cell Institute and the Institute for Medical Research of the University of Cambridge, have identified important differentiation pathways of stem cells. The Munich scientists were responsible for the characterization of transcriptional networks in blood stem and progenitor cells using high-throughput single-cell gene expression analysis.

Out of a pool of nearly 600 single primary blood stem and progenitor cells isolated from mouse bone marrow, 18 transcription factors were identified which can cause a further differentiation of the progenitor stem cells. Transcription factors are responsible for turning gene expression “on” or “off”. By means of a statistical mapping technique known as dimensionality reduction, Florian Büttner and Fabian Theis identified specific patterns in the pairings of these transcription factors. The pairings could be correlated positively or negatively with characteristic stages of cell maturation and therefore provided clues about the functions of the individual transcription factors and the cell fate. Within the expression patterns, the scientists also found previously unrecognized relationships between the factors Gata2, Gfi1 and Gfi1b. This is of particular importance because especially for Gata2 and Gfi1, recently a correlation has been described with leukemia: Gata2 is thought to promote the formation of malignant cell clones, whereas Gfi1 plays a more protective role.
The reconstruction of individual transcription factor profiles and the identification of their networks offer the opportunity not only to under­stand the physiological differentiation and development of cells, but to better understand degenerative and malignant processes.

Cell differentiation is regulated by a complex interaction of ­external influences on the internal cell environment, in which so-called transcription factor-regulated-networks are of particular importance. Transcription factors are responsible for activating or repressing gene expression.

Netzwerk von 18 Transkriptionsfaktoren, die an der Differenzierung von Knochenmarks-Stammzellen zu verschiedenen Blut- und Immunzellen beteiligt sind. Quelle: HMGU