associated project

/project 6

Category: .projects
M. Kieslinger, Munich

Determining the supporting mesenchymal cell lineages and their interactions with multiple myeloma

Various tumor cells, including those from hematopoietic malignancies, home to the bone marrow and interact with osteoblasts and osteoclasts, disrupting normal bone biology and hematopoiesis. As the most immature hematopoietic cells are affected in most cases, and osteoblasts are part of their supportive microenvironment, it is likely that the tumor cells interfere with these niche cells. Our group has identified a subset of osteoblastic cells (IEO) as a niche for hematopoietic stem cells, and is able to identify and isolate those in vivo.
The aim of this project is to investigate if IEO cells define a niche also for tumour cells in the bone marrow and are functionally required for this supportive role. To date, we have identified a novel secreted protein of 17kDA that is secreted by IEO cells and that is necessary for the support of normal hematopoietic stem cells. This protein is already implicated in the proliferation of cells from several different tumor types, and we are now investigating if this function is provided by IEO cells.

Dr. rer. nat. Matthias Kieslinger began his work on the differentiation of normal and malignant hematopoietic cells and has later extended his focus on bone biology. He started his own research group at the institute of clinical molecular biology and tumor genetics at the Helmholtz Center in Munich and is examining the interplay between these two fields.

Project-related list of publications

Jin S, Kim J, Willert T, Klein-Rodewald T, Garcia-Dominguez M, Mosqueira M, Fink R, Esposito I, Hofbauer LC, Charnay P, Kieslinger M. Ebf factors and MyoD synergistically regulate muscle relaxation via Atp2a1. Nature Comm 2014; in press.

Kim J, Badaloni A, Willert T, Zimber-Strobl U, Kühn R, Wurst W, Kieslinger M. A miRNA-based approach to down-regulate a gene family in vivo. PLOS One 2013;8:80312.

Kieslinger M, Hiechinger S, Dobreva G, Consalez GG, Grosschedl R. Early B cell factor 2 regulates homeostasis of hematopoietic stem cells in a cell non-autonomous manner. Cell Stem Cell 2010;7:496-507.
Dolznig H, Grebien F, Deiner EM, Stangl K, Kolbus A, Habermann B, Kerenyi MA, Kieslinger M, Moriggl R, Beug H, Müllner EW. Erythroid progenitor renewal versus differentiation: genetic evidence for cell autonomous, essential functions of EpoR, Stat5 and the GR. Oncogene 2006;25:2890-2900.
Kieslinger M, Folberth S, Dobreva G, Dorn T, Croci L, Erben R, Consalez GG, Grosschedl R. EBF2 Regulates osteoblast-dependent differentiation of osteoclasts. Dev Cell 2005;9:757-767.
Medina KL, Pongubala JM, Reddy KL, Lancki DW, Dekoter R, Kieslinger M, Grosschedl R, Singh H. Assembling a gene regulatory network for specification of the B cell fate. Dev Cell 2004;7:607-617.
Kieslinger M, Woldman I, Moriggl R, Hofmann J, Marine JC, Ihle JN, Beug H, Decker T. Antiapoptotic activity of Stat5 required during terminal stages of myeloid differentiation. Genes Dev 2000;14:232-244.
Dahl R*, Kieslinger M*, Beug H, Hayman MJ. Transformation of hematopoietic cells by the Ski oncoprotein involves repression of retinoic acid receptor signaling. Proc Natl Acad Sci USA 1998;95:11187-11192. (*equal contribution)

Technische Universitt Dresden    Christian-Albrechts-Universitt zu Kiel    Julius-Maximilians-Universitt Wrzburg
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