Previously, extensive research has focused on hematopoietic stem cells (HSCs) and distinct multipotent progenitor populations (MPP1-4) contained within the Lin- Sca-1+ c-Kit+ (LSK) compartment. In this new study, researchers around Pia Sommerkamp now phenotypically define and functionally characterize MPP5 (LSK CD34+ CD135- CD48- CD150-), a novel subset in the progenitor landscape. The team, which involved colleagues at the Max-Planck Institute in Freiburg, at the Institute Curie in Paris and at Harvard University, reports that MPP5 provide initial emergency myelopoiesis followed by stable contribution to the lymphoid lineage in transplantation settings. Using different in vitroand in vivo approaches as well as RNA-seq and single-cell (sc) RNA-seq analysis, MPP5 were shown to represent a hub within the MPP network.

The work 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 in Freiburg, and was published in Blood.

 

 

Further Reading:

Publication: Sommerkamp, P., Romero-Mulero, M. C., Narr, A., Ladel, L., Hustin, L., Schonberger, K., Renders, S., Altamura, S., Zeisberger, P., Jacklein, K., Klimmeck, D., Rodriguez-Fraticelli, A., Camargo, F. D., Perie, L., Trumpp, A. & Cabezas-Wallscheid, N. (2021) Mouse multipotent progenitor 5 cells are located at the interphase between hematopoietic stem and progenitor cells, Blood. 137, 3218-3224. doi: 10.1182/blood.2020007876 PMID: 33754628

A new method called MutaSeq allows stem cells and cancer stem cells to be studied at the single cell level and the resulting cell clones to be traced directly. The method was developed by scientists from HI-STEM, the German Cancer Research Center (DKFZ), the European Molecular Biology Laboratory (EMBL) and the Center for Genome Regulation in Barcelona. Studying thousands of individual cells in parallel, the researchers combined the analysis of the genomic cancer mutations with the associated expression profiles.

Further Reading:

  • Publication: Velten L, Story BA, Hernández-Malmierca P, Raffel S, Leonce DR, Milbank J, Paulsen M, Demir A, Szu-Tu C, Frömel R, Lutz C, Nowak D, Jann JC, Pabst C, Boch T, Hofmann WK, Müller-Tidow C, Trumpp A, Haas S, Steinmetz LM. Identification of leukemic and pre-leukemic stem cells by clonal tracking from single-cell transcriptomics. Nature Communication. 2021 Mar 1;12(1):1366. doi: 10.1038/s41467-021-21650-1. PMID: 33649320; PMCID: PMC7921413.
  • DKFZ Press Release

Isolation of epithelial cells form fresh PDAC patient tissues and normal pancreas for analysis of transcriptome and whole genome methylome. (c): Elisa Espinet

In a study led by HI-STEM researcher Elisa Espinet, HI-STEM researchers teamed up with an interdisciplinary group of clinicians, bioinformaticians and biomedical researchers to shed more light on the reasons for the heterogenous aggressiveness of different pancreatic tumors.

They were able to define two differently aggressive molecular subtypes of pancreatic carcinoma based on the DNA-methylome of the tumor cells, providing new insights into the origin of the tumors. In the more aggressive group of tumors, a phenomenon known as "viral mimicry" leads to a cancer-promoting inflammatory reaction. This could possibly be the basis for the development of a targeted, subtype-oriented therapy. The results have now been published in the journal Cancer Discovery.

 Read more:

  • Original Publication: Elisa Espinet, Zuguang Gu, Charles D. Imbusch, Nathalia A. Giese, Magdalena, Büscher, Mariam Safavi, Silke Weisenburger, Corinna Klein, Vanessa Vogel, Mattia Falcone, Jacob Insua-Rodríguez, Manuel Reitberger, Vera Thiel, Steffi O. Kossi, Alexander Muckenhuber, Karnjit Sarai, Alex YL Lee, Elyne Backx, Soheila Zarei, Matthias M. Gaida, Manuel Rodríguez-Paredes, Elisa Donato, Hsi-Yu Yen, Roland Eils, Matthias Schlesner, Nicole Pfarr, Thilo Hackert, Christoph Plass, Benedikt Brors, Katja Steiger, Dieter Weichenhan, H. Efsun Arda, Ilse Rooman, Janel L. Kopp, Oliver Strobel, Wilko Weichert, Martin R. Sprick* and Andreas Trumpp*: Aggressive PDACs show hypomethylation of repetitive elements and the Execution of an intrinsic IFN program linked to a ductal Cell of origin Cancer Discovery 2020, DOI: 1158/2159-8290.CD-20-1202
  • DKFZ Press Release (German Version)
  • Twitter Thread by Elisa Espinet summarizing the results: https://twitter.com/ElisaEspinet/status/1316781872303820800
  • Altmetric Page for the Article: https://www.altmetric.com/details/92452310

A characteristic feature of all stem cells is their ability to self-renew. But how is this potential maintained throughout life? Scientists at the German Cancer Research Center (DKFZ) and the Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM) have now discovered in mice that cells in the so-called "stem cell niche" are responsible for this: Blood vessel cells of the niche produce a factor that stimulates blood stem cells and thus maintains their self-renewal capacity. With the decades of life, the production of this factor ceases and blood stem cells begin to age.

The work was led by Simon Renders, a MD-PhD Student who carried out his PhD thesis in the HI-STEM lab.

Read more:

  • Original Publication: Renders, S., Svendsen, A. F., Panten, J., Rama, N., Maryanovich, M., Sommerkamp, P., Ladel, L., Redavid, A. R., Gibert, B., Lazare, S., Ducarouge, B., Schönberger, K., Narr, A., Tourbez, M., Dethmers-Ausema, B., Zwart, E., Hotz-Wagenblatt, A., Zhang, D., Korn, C., Zeisberger, P., Przybylla, A., Sohn, M., Mendez-Ferrer, S., Heikenwälder, M., Brune, M., Klimmeck, D., Bystrykh, L., Frenette, P. S., Mehlen, P., de Haan, G., Cabezas-Wallscheid, N.*, & Trumpp, A.* (2021). Niche derived netrin-1 regulates hematopoietic stem cell dormancy via its receptor neogenin-1. Nature Communications, 12(1), 608. 10.1038/s41467-020-20801-0
  • DKFZ Press Release / DKFZ Pressemitteilung

Phd Defense of Pia Sommerkamp (middle) with her supervisors Andreas Trumpp and Nina Cabezas-Wallscheid

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).

  1. 8th GSCN Conference - goes virtual
  2. Hidden messages in mRNA transcripts: Alternative polyadenylation (APA) is a novel control mechanism enabling hematopoietic stem cells (HSC) to adapt their activity to emergency situations– new publication in Cell Stem Cell
  3. How tumor cells create a metastatic niche – new work from the Oskarsson lab published in Nature Communications
  4. LeukoSystem: New BMBF-funded eMed Junior Consortium to investigate leukaemia causes and therapies
  5. German Cancer Prize Awarded to Andreas Trumpp
  6. New paper out on Nature Cell Biology: 3D atlas of the bone marrow - in single cell resolution
  7. Andreas Trumpp recognized as Highly Cited Researcher 2019
  8. ÜBERLEBENSSTRATEGIEN: Science Communication Event with colleagues from the Stem Cell SFB (CRC873)
  9. Mick elected into representative roles within both EHA and ASH.
  10. Making cancer stem cells visible to the immune system - New results may enable innovative treatment concept against leukemia (New publication in Nature)
  11. A new tool to study hematopoiesis in detail: Optimized multicolor immunofluorescence panel differentiating major steps of blood development published in Cytometry (OMIP‐059)
  12. Her Honour Lieutenant Governor of Ontario Elizabeth Dowdeswell visits HI-STEM

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