Deficiency of Lipid Phosphatase SHIP Enables Long-Term Reconstitution of Hematopoietic Inductive Bone Marrow Microenvironment
Date
2013
Author(s)
Lu, Jiayun
Nombela-Arrieta, César
Zhao, Li
Pivarnik, Gregory
Mondal, Subhanjan
Publisher
Elsevier BV
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Citation
Liang, Olin Dehui, Jiayun Lu, César Nombela-Arrieta, Jia Zhong, Li Zhao, Gregory Pivarnik, Subhanjan Mondal, Li Chai, Leslie E. Silberstein, and Hongbo R. Luo. 2013. “Deficiency of Lipid Phosphatase SHIP Enables Long-Term Reconstitution of Hematopoietic Inductive Bone Marrow Microenvironment.” Developmental Cell 25 (4) (May): 333–349. doi:10.1016/j.devcel.2013.04.016. http://dx.doi.org/10.1016/j.devcel.2013.04.016.
Abstract
A dysfunctional bone marrow (BM) microenvironment is thought to contribute to the development of hematologic diseases. However, functional replacement of pathologic BM microenvironment through BM transplantation has not been possible. Furthermore, the study of hematopoietic inductive BM microenvironment is hampered by the lack of a functional nonhematopoietic reconstitution system. Here, we show that a deficiency of SH2-containing inositol-5'-phosphatase-1 (SHIP) in a nonhematopoietic host microenvironment enables its functional reconstitution by wild-type donor cells. This microenvironment reconstitution normalizes hematopoiesis in peripheral blood and BM and alleviates pathology of spleen and lung in the SHIP-deficient recipients. SHIP-deficient BM contains a significantly smaller population of multipotent stromal cells with distinct properties, which may contribute to the reconstitution by wild-type cells. We further demonstrate that it is the nonhematopoietic donor cells that are responsible for the reconstitution. Thus, we have established a nonhematopoietic BM microenvironment reconstitution system to functionally study specific cell types in hematopoietic niches.
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