Mesenchymal stem/progenitor cells promote the reconstitution of exogenous hematopoietic stem cells in Fancg-/- mice in vivo.
Fanconi anemia (FA) is a heterogeneous genetic disorder characterized by bone marrow failure and complex congenital anomalies. Although mutations in FA genes result in a characteristic phenotype in the hematopoietic stem/progenitor cells (HSPCs), little is known about the consequences of a nonfunctional FA pathway in other stem/progenitor cell compartments. Given the intense functional interactions between HSPCs and the mesenchymal microenvironment, we investigated the FA pathway on the cellular functions of murine mesenchymal stem/progenitor cells (MSPCs) and their interactions with HSPCs in vitro and in vivo. Here, we show that loss of the murine homologue of FANCG (Fancg) results in a defect in MSPC proliferation and in their ability to support the adhesion and engraftment of murine syngeneic HSPCs in vitro or in vivo. Transplantation of wild-type (WT) but not Fancg(-/-) MSPCs into the tibiae of Fancg(-/-) recipient mice enhances the HSPC engraftment kinetics, the BM cellularity, and the number of progenitors per tibia of WT HSPCs injected into lethally irradiated Fancg(-/-) recipients. Collectively, these data show that FA proteins are required in the BM microenvironment to maintain normal hematopoiesis and provide genetic and quantitative evidence that adoptive transfer of WT MSPCs enhances hematopoietic stem cell engraftment.
Li
Yan
Y
Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Chen
Shi
S
Yuan
Jin
J
Yang
Yanzhu
Y
Li
Jingling
J
Ma
Jin
J
Wu
Xiaohua
X
Freund
Marcel
M
Pollok
Karen
K
Hanenberg
Helmut
H
Goebel
W Scott
WS
Yang
Feng-Chun
FC
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001853:Bone Marrow / Q000502:physiology; D002448:Cell Adhesion / Q000502:physiology; D049109:Cell Proliferation; D052241:Fanconi Anemia Complementation Group G Protein / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry; D006410:Hematopoiesis / Q000502:physiology*; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D006801:Humans; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051379:Mice; D008817:Mice, Mutant Strains
C499910:Fancg protein, mouse; D052241:Fanconi Anemia Complementation Group G Protein