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

Autor: Marie-Dominique Filippi, Rupali Sani Kumar, Ramesh C. Nayak, Rachna Raman, Kathleen Szczur, Jose A. Cancelas, Juying Xu, Sachin Kumar, Ashwini Hinge
Jazyk: angličtina
Rok vydání: 2013
Předmět:
Cancer Research
Pathology
Cellular differentiation
Mice
0302 clinical medicine
Adipocytes
mesenchymal stem cell
Cells
Cultured
Mice
Knockout
0303 health sciences
Stem Cells
GTPase-Activating Proteins
Osteoblast
Wnt3a
Cell Differentiation
Hematology
Flow Cytometry
Cell biology
Haematopoiesis
medicine.anatomical_structure
Oncology
Cellular Microenvironment
Stem cell
p190-B RhoGAP
medicine.medical_specialty
Bone Marrow Cells
Biology
Real-Time Polymerase Chain Reaction
Article
Bone and Bones
03 medical and health sciences
Fetus
medicine
Animals
Progenitor cell
030304 developmental biology
Osteoblasts
Mesenchymal stem cell
Mesenchymal Stem Cells
Fibroblasts
Hematopoietic Stem Cells
microenvironment
hematopoiesis
Transplantation
Mice
Inbred C57BL
Wnt Proteins
Bone marrow
Stromal Cells
030217 neurology & neurosurgery
Spleen
Zdroj: Leukemia
ISSN: 1476-5551
0887-6924
Popis: 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.
Databáze: OpenAIRE
Externí odkaz: