Characterization of the transcription factor Gfi1 as novel regulator of bone homeostasis

• Applicant: Professor Dr. Stefan Mundlos
• Subject Area: Rheumatology
• Term: from 2010 to 2015
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 169478868

The transcription factor growth factor independent 1 (GFI1) is a negative regulator of hematopoietic stem cell (HSC) proliferation. Loss of Gfi1 induces neutropenia, lymphocyte deficiency, and monocyte accumulation. It is well established that the HSC pool is regulated by osteoblasts; however, whether HSC regulate osteoblasts or MSC differentiation is poorly characterized. We demonstrate that Gfi1 knock-out mice (Gfi1-/-) show a progressive bone loss (osteoporosis), which is in line with the osteoporotic phenotype in patients suffering from chronic idiopathic neutropenia. This project aims to define the underlying mechanism of osteoporosis in Gfi1-/- mice. Moreover, we intend to characterize the influence of a presumably altered HSC pool on osteoblasts within the stem cell niche in Gfi1-/- mice.

• DFG Programme: Priority Programmes
• Subproject of: SPP 1468: Osteoimmunology - IMMUNOBONE - A Programme to Unravel the Mutual Interactions between the Immune System and Bone
• Participating Person: Professor Dr. Uwe Kornak