The transcription factor Nanog plays a crucial role within the self-renewal of embryonic stem cells. Previously unclear had been how its protein abundance is regulated in the cellular material. Researchers at the Helmholtz Zentrum Mü nchen and the Specialized University of Munich, working in collaboration with colleagues through ETH Zü rich, now report in Cell Systems that the more Nanog there is certainly on hand, the less reproduction there is.

Every stem cell researcher knows the particular protein Nanog because it ensures that these all-rounders continue to restore. A controversial debate revolved around how the quantity of Nanog protein in the cell is regulated. “So far it had been often assumed that Nanog activates itself in order to protect the pluripotency in embryonic stem cells, ” clarifies Dr . Carsten Marr. He heads the Quantitative Individual Cell Dynamics research group at the Institute of Computational Biology (ICB) of the Helmholtz Zentrum Mü nchen. Along with colleagues from ETH Zü rich, he and his group have developed an algorithm called STILT (Stochastic Inference on Family tree Trees) that now rebuts this assumption.

Using STILT, the scientists evaluated time-resolved protein appearance data (already collected in 2015) from individual tissue in which Nanog could be detected through fusion with a fluorescence protein. “We compared the Nanog dynamics that were assessed in this way with three different models. One of the challenges here was your quantitative comparison of the models, and another was getting stem cell divisions into account in the algorithm, ” reviews first author Dr . Justin Feigelman, who had transferred from the Helmholtz Zentrum Mü nchen to ETH Zü rich as a postdoc. “The results show that Nanog is regulated by a so-called negative feedback loop, meaning that the more Nanog there is in the cells, the less duplication there will be. ”

Carried over through the computer to the petri dish

To be able to check these results, the scientists calculated what happens if there were an artificial increase in Nanog protein ranges. “We then actually succeeded in confirming the speculation put forward by STILT in an additional single-cell experiment with improved Nanog, ” explains study leader Marr.

Thanks to their research, the scientists promise a better knowing for stem cell renewal and hope that this understanding might be useful for medical applications in the future. “We will also be using STILT to other time-resolved single cell data in the future, that will give us insight into the underlying molecular gene regulation systems, ” Marr explains.

The STILT application is freely available to other scientists on the Internet: www.imsb.ethz.ch/research/claassen/Software/stilt — stochastic-inference-on-lineage-trees. html

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Materials provided by Helmholtz Zentrum Muenchen – German Research Center for Environmental Health . Note: Articles may be edited for style and length.