Comparison of gene expression of BMDM and microglia

Description

Work by Marco Prinz and colleagues defined bone-marrow derived CCR2⁺ myeloid cells as direct precursor cells of BMDM and described the local conditions within the brain that are necessary for monocyte engraftment into the CNS. However, these BMDM are clearly postnatally derived and distinct from yolk sac-derived microglia. Whether BMDM and microglia have the same functional features and fates is not yet known. One major issue is therefore to determine the functional similarities and dissimilarities of BMDM as compared to microglia during brain diseases such as stroke and neurodegeneration. For this purpose BMDM and microglia will be sorted, their transcriptional profiles will be examined, and relevant factors will be characterized. This project will help to design further studies for the selective activation and recruitment of myeloid cells either to or within the brain. Recruitment of myeloid cells will be studied in cooperation with partner 10. Results obtained in this project on the gene expression in myeloid cells will provide important information for the projects of partners 6, 9, and 11.

Publications:

• Dann A, Poeck H, Croxford A, Gaupp S, Kierdorf K, Knust M, Pfeifer D, Maihoefer C, Endres S, Kalinke U, Meuth S, Wiendl H, Knobeloch KP, Akira S, Waisman A, Hartmann G, Prinz M (2011) Cytosolic RIG-I-like helicases act as negative regulators of sterile inflammation of the CNS. Nat Neurosci. doi: 10.1038/nn.2964.
• Prinz M*, Schmidt H, Mildner A, Knobeloch KP, Hanisch UK, Raasch J, Merkler D, Detje C, Gutcher I, Mages J, Lang R, Martin R, Gold R, Becher B, Brück W, Kalinke U (2008) Distinct and non-redundant in vivo functions of IFNAR on myeloid cells limit autoimmunity

Tasks and methodology:

•          BMDM and microglia will be sorted

•          Transcriptional profiling

•          Immunohistochemistry, Western blotting, quantitative PCR

Planned secondment:

Medeia Therapeutics Ltd. , Generation of tools to track BMDM, 8 month