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

转录因子生长因子独立1 （GFI1）是造血干细胞（HSC）增殖的负调控因子。Gfi1的缺失导致中性粒细胞减少、淋巴细胞缺乏和单核细胞积聚。已经确定的是，造血干细胞库是由成骨细胞调节的；然而，HSC是否调节成骨细胞或MSC分化的特征尚不明确。我们证明Gfi1敲除小鼠（Gfi1-/-）表现出进行性骨质流失（骨质疏松症），这与慢性特发性中性粒细胞减少症患者的骨质疏松表型一致。本项目旨在明确Gfi1-/-小鼠骨质疏松的潜在机制。此外，我们打算表征可能改变的HSC池对Gfi1-/-小鼠干细胞生态位内成骨细胞的影响。

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.