Pia Sommerkamp, who carried out her PhD at HI-STEM and the Division of Stem Cells and Cancer at the DKFZ until July 2019, has been awarded the Wilma-Moser Prize of Heidelberg University. The award annually honors the youngest female doctoral candidate finishing the PhD with distinction (“summa cum laude”) within the faculties of Medicine and Natural Sciences, Mathematics, and Computer Sciences. Pia defended her PhD in July 2019 and is currently continuing her work as a Postdoc at HI-STEM. 

As part of her PhD, which was jointly supervised by Nina Cabezas-Wallscheid and Andreas Trumpp, Pia Sommerkamp could show that alternative polyadenylation (APA) is a novel molecular control mechanism used by hematopoietic stem cells (HSC) to adapt their metabolic and proliferative activity to emergency situations. Her PhD work was published in Cell Stem Cell (2020) and in Scientific Reports (2019).

A team of researchers around Pia Sommerkamp, who carried out her PhD thesis in the HI-STEM lab and now continues as a Postdoc, now reports alternative polyadenylation (APA) as a new layer of gene regulation. In their study, the team, which involved colleagues at the Max-Planck Institute in Freiburg and at Heidelberg University Hospital, reports APA as a new, so far unrecognized, layer of regulation of HSCs active during homeostasis and in response to emergency situations such as inflammation.

APA is a process that mediates selection of polyadenylation sites in mRNAs. It thereby regulates RNA/protein isoform expression and the length of the untranslated region of the mRNA (3’ UTR). Our study now demonstrates that the RNA regulatory mechanism APA is dynamically regulated within the hematopoietic stem cell and progenitor compartment. We could show that unperturbed APA is essential for proper HSC function. Using a novel sequencing approach to characterize the 3’ UTR in a genome-wide manner, it was possible to determine alternative polyadenylation landscapes (“APAomes”) in resting and activated HSCs, revealing distinct APA profiles and 3’ UTR length patterns. In addition, we show that metabolic reprogramming by APA is a prerequisite for HSC function in emergency situations. In the future, we will investigate whether APA regulation is also active in cancer stem cells, e.g. in leukemia, in order to evaluate possible ways to specifically interfere with this regulation in disease.

The work, which was published in Cell Stem Cell, was co-supervised by Andreas Trumpp from HI-STEM/DKFZ and Nina Cabezas-Wallscheid, HI-STEM Alumni and now a junior group leader at the Max-Planck-Institute of Immunobiology.

Read more:

• Original Publication: Pia Sommerkamp, Sandro Altamura, Simon Renders, Andreas Narr, Luisa Ladel, Petra Zeisberger, Paula Leonie Eiben, Malak Fawaz, Michael A. Rieger, Nina Cabezas-Wallscheid und Andreas Trumpp: Differential alternative polyadenylation landscapes mediate hematopoietic stem cell activation and regulate glutamin metabolism.Cell Stem Cell 2020, DOI: 10.1016/j.stem.2020.03.003
• DKFZ Press Release (German Version)

The German Stem Cell Network (GSCN) aims to foster basic and applied stem cell research in Germany. HI-STEM is happy to forward the invitation by the GSCN to their 8^th Annual Conference. The conference will be held from 23 - 25 September 2020 in a virtual format.

Further information: https://gscn-conferences.org/

In order to colonize other organs and grow into metastases, tumor cells that detach from the parent tumor need to manipulate their new microenvironment and create a 'metastatic niche'. Maren Pein and colleagues from the Oskarsson lab within HI-STEM and DKFZ have now discovered that disseminated breast cancer cells evoke phenotypic changes in lung fibroblasts to promote metastasis. This discovery, which is based on a collaboration with clinical partners at the National Center for Tumor Diseases (NCT) and the University Hospital in Heidelberg, plays a key role in better understanding how these dangerous metastases arise.

Read more:

• Original Paper: Pein, M., Insua-Rodríguez, J., Hongu, T., Riedel, A., Meier, J., Wiedmann, L., Decker, K., Essers, M. A. G., Sinn, H. P., Spaich, S., Sutterlin, M., Schneeweiss, A., Trumpp, A. and Oskarsson, T. (2020). Metastasis-initiating cells induce and exploit a fibroblast niche to fuel malignant colonization of the lungs. Nature Communications, 11(1), 1494. DOI: 10.1038/s41467-020-15188-x
• DKFZ Press Release | German Version
• Feature in at Ärzteblatt.de: https://www.aerzteblatt.de/nachrichten/111618/Strategien-von-Tumorzellen-zur-Metastasenbildung