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Normal Hemopoiesis

p190-B RhoGAP regulates the functional composition of the mesenchymal microenvironment

Leukemia volume 27, pages 2209–2219 (2013)Cite this article

Abstract

Hematopoiesis is regulated by components of the microenvironment, so-called niche. Here, we show that p190-B GTPase-activating protein (p190-B) deletion in mice causes hematopoietic failure during ontogeny, in p190-B−/− fetal liver and bones, and in p190-B+/− adult bones and spleen. These defects are non-cell autonomous, as we previously showed that transplantation of p190-B−/− hematopoietic cells into wild-type (WT) hosts leads to normal hematopoiesis. Coculture of mesenchymal stem (MSC)/progenitor cells and wild-type bone marrow (BM) cells reveals that p190-B−/− MSCs are dysfunctional in supporting hematopoiesis owing to impaired Wnt signaling. Furthermore, p190-B loss causes alteration in BM niche composition, including abnormal colony-forming unit (CFU)-fibroblast, CFU-adipocyte and CFU-osteoblast numbers. This is due to altered MSC lineage fate specification to osteoblast and adipocyte lineages. Thus, p190-B organizes a functional mesenchymal/microenvironment for normal hematopoiesis during development.

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Acknowledgements

We thank the mouse core, Jeff Bailey and Victoria Summey, for BM transplantation and the flow cytometry core for assistance with cell sorting at Cincinnati Children’s Hospital Medical Center. The work was supported by NIH (HL090676 and HL104458-MDF).

Author contributions

R Raman designed and performed experiments, analyzed the data and wrote the paper; RS Kumar and A Hinge designed and performed experiments, and analyzed the data; S Kumar, R Nayak, J Xu, K Szczur performed experiments; J A Cancelas provided key advice in research design, data analysis and editing the paper; M-D Filippi designed and directed the program research, analyzed data, and wrote and edited the manuscript.

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  1. R Raman, R S Kumar and A Hinge: These authors equally contributed to the work.

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  1. Division of Experimental Hematology and Cancer Biology, Cincinnati Children’s Research Foundation, University of Cincinnati College of Medicine, Cincinnati, OH, USA

    R Raman, R S Kumar, A Hinge, S Kumar, R Nayak, J Xu, K Szczur, J A Cancelas & M-D Filippi

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Raman, R., Kumar, R., Hinge, A. et al. p190-B RhoGAP regulates the functional composition of the mesenchymal microenvironment. Leukemia 27, 2209–2219 (2013). https://doi.org/10.1038/leu.2013.103

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