Xiaoxiao Li, HoangDinh Huynh, Hao Zuo, Marjo Salminen, and Yihong Wan
Gata2 is a zinc finger transcription factor that is important in hematopoiesis and neuronal development. However, the roles of Gata2 in the mesenchymal lineages are poorly understood. In vitro studies suggest that Gata2 modulates adipocyte differentiation and mesenchymal stem cells (MSC) proliferation. To systematically determine the in vivo functions of Gata2 in MSC lineage commitment and development, we have generated three mouse models where Gata2 is specifically deleted in MSC, adipocyte or osteoblast. During MSC expansion stage, Gata2 promotes proliferation and attenuates differentiation; thereby Gata2 loss in MSC results in enhanced differentiation of both adipocyte and osteoblast. During differentiation stage, Gata2 also plays MSC-independent roles to impede lineage commitment; hence Gata2 loss in adipocyte or osteoblast lineages also augments adipogenesis and osteoblastogenesis, respectively. These findings reveal Gata2 as a crucial rheostat of MSC fate to control osteoblast and adipocyte lineage development.