Stem Cell and Macrophage Biology
Previous and Current Research
Our research is located at the interface of immunology and stem cell research and 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 to protect transplant recipients from lethal infections. Furthermore, we discovered that macrophages, mature cells of the immune system, can activate a network of genes shared with embryonic stem cells that enables them to proliferate indefinitely. Based on these discoveries macrophages can be amplified in culture as mature differentiated cells, without stem cell intermediates or tumorigenic transformation. Our results show the compatibility of self-renewal and differentiation and open the door for new macrophage based therapies.
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)