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Cell and Macrophage Biology - Michael Sieweke

Human bodies are continually changing and the fact that stem cells are able to regenerate themselves means that in most tissue - be it in the intestines, the skin or the blood - new cells are constantly being created too. This is the way the tissue is preserved or heals after injury. The Sieweke group will focus on mechanisms of blood formation and could help to develop possible new approaches to cellular therapy.

 

Figure: Macrophages seen from above.

Previous and current research

Our recent findings lay the groundwork for new cellular therapy approaches in regenerative medicine.

One important line of our work has revealed mechanisms how hematopoietic stem cells can generate more myeloid cells, including macrophages, to protect transplant recipients from lethal infections.

Furthermore, we discovered that macrophages, mature cells of the immune system, could activate a network of self-renewal genes shared with embryonic stem cells that enables them to proliferate indefinitely. This makes it possible to amplify macrophages in culture as mature differentiated cells, without stem cell intermediates or tumorigenic transformation. Our results show that not only stem cells but also mature cells like macrophages can activate self-renewal mechanisms. This opens the door for new macrophage-based therapies.

Future projects and goals

We will investigate how the endogenous capacity of blood stem cells to produce myeloid cells like macrophages can be enhanced for clinical applications where insufficient production of these cells leads to immune depression and potentially fatal infections.

We want to understand what controls how many times a cell can divide and how this ability can be extended without turning the cell into a tumour cell. We are translating such findings from mouse models to extend the life span and amplify human macrophages.

We are developing gene-editing capacities in macrophages that will enable us to tailor macrophage cellular therapies to specific needs in regenerative medicine and for the modulation of the immune system.

We believe that the understanding and manipulation of macrophages will be instrumental to slow, halt or even revert successive degeneration occurring with advanced age in organs like the heart, the brain and the lung by re-activating juvenile regeneration mechanisms.

Selected publications

Matcovitch-Natan O, Winter DR, Giladi A, Vargas Aguilar S, Spinrad A, Sarrazin S, Ben-Yehuda H, David E, Zelada Gonzalez F, Perrin P, Keren-Shaul H, Gury M, Lara-Astaiso D, Thaiss CA, Cohen M, Halpern KB, Baruch K, Deczkowska A, Lorenzo-Vivas E, Itzkovitz S, Elinav E, Sieweke MH*, Schwartz M*, Amit I*
Microglia development follows a stepwise program to regulate brain homeostasis.
Science 353, aad8670. (2016) [* equal contribution]

Soucie EL, Wenig W, Geirsdóttir L, Molawi K, Maurizio J, Fenouil R, Mossadegh-Keller N, Gimenez G, VanHille L, Beniazza M, Favret J, Berruyer C, Perrin P, Hacohen N, Andrau JC, Ferrier P, Dubreuil P, Sidow A, Sieweke MH
Lineage-specific enhancers activate self-renewal genes in macrophages and embryonic stem cells.
Science 351, aad5510 (2016)

Mossadegh-Keller N, Sarrazin S, Kandalla PK, Espinosa L, Stanley RE, Nutt SL, Moore J, Sieweke MH
M-CSF instructs myeloid lineage fate in single haematopoietic stem cells.
Nature 9, 239–243 (2013)

Aziz A, Soucie E, Sarrazin S, Sieweke MH
MafB/c-Maf deficiency enables self-renewal of differentiated functional macrophages.
Science 326, 867–871 (2009)

Sarrazin S, Mossadegh-Keller N, Fukao T, Aziz A, Mourcin F., Kelly L, Vanhille L, Kastner P, Chan S, Duprez E, Otto, C, Sieweke MH
MafB restricts M-CSF dependent myeloid commitment divisions of hematopoietic stem cells.
Cell 138, 300–313 (2009)

Group members

Contact

Group Leader

Prof. Dr. Michael H. Sieweke

Assistant to Group Leader

Jeannette Hoppe

Phone: +49 (0)351 458 82000