title: p190-B RhoGAP regulates the functional composition of the mesenchymal microenvironment.
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.
authors.affiliation: Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Research Foundation, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
authors.forename: R
authors.initials: R
authors.lastname: Raman
authors.forename: R S
authors.initials: RS
authors.lastname: Kumar
authors.forename: A
authors.initials: A
authors.lastname: Hinge
authors.forename: S
authors.initials: S
authors.lastname: Kumar
authors.forename: R
authors.initials: R
authors.lastname: Nayak
authors.forename: J
authors.initials: J
authors.lastname: Xu
authors.forename: K
authors.initials: K
authors.lastname: Szczur
authors.forename: J A
authors.initials: JA
authors.lastname: Cancelas
authors.forename: M-D
authors.initials: MD
authors.lastname: Filippi
mesh_terms: D017667:Adipocytes / Q000166:cytology* / Q000378:metabolism; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology* / Q000378:metabolism; D001842:Bone and Bones / Q000166:cytology / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D060833:Cellular Microenvironment; D005333:Fetus; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D005434:Flow Cytometry; D020690:GTPase-Activating Proteins / Q000502:physiology*; D006410:Hematopoiesis / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D013154:Spleen / Q000166:cytology / Q000378:metabolism; D013234:Stem Cells; D017154:Stromal Cells / Q000166:cytology / Q000378:metabolism; D051153:Wnt Proteins / Q000378:metabolism
chemical_list: C513042:Arhgap5 protein, mouse; D020690:GTPase-Activating Proteins; D051153:Wnt Proteins
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