Format

Send to

Choose Destination
Hum Mol Genet. 2012 Jan 1;21(1):121-35. doi: 10.1093/hmg/ddr447. Epub 2011 Oct 3.

Impaired functionality and homing of Fancg-deficient hematopoietic stem cells.

Author information

1
Laboratoire de Gamétogenèse Apoptose et Génotoxicite, Institut de Radiobiologie Cellulaire et Moléculaire, Direction des Sciences du Vivant, Commissariat à l'Energie Atomique et aux Energies Alternatives, Fontenay-aux-Roses 92265, France.

Abstract

Fanconi anemia (FA) is a human rare genetic disorder characterized by congenital defects, bone marrow (BM) failure and predisposition to leukemia. The progressive aplastic anemia suggests a defect in the ability of hematopoietic stem cells (HSC) to sustain hematopoieis. We have examined the role of the nuclear FA core complex gene Fancg in the functionality of HSC. In Fancg-/- mice, we observed a decay of long-term HSC and multipotent progenitors that account for the reduction in the LSK compartment containing primitive hematopoietic cells. Fancg-/- lymphoid and myeloid progenitor cells were also affected, and myeloid progenitors show compromised in vitro functionality. HSC from Fancg-/- mice failed to engraft and to reconstitute at short and long term the hematopoiesis in a competitive transplantation assay. Fancg-/- LSK cells showed a loss of quiescence, an impaired migration in vitro in response to the chemokine CXCL12 and a defective homing to the BM after transplantation. Finally, the expression of several key genes involved in self-renewal, quiescence and migration of HSC was dysregulated in Fancg-deficient LSK subset. Collectively, our data reveal that Fancg should play a role in the regulation of physiological functions of HSC.

PMID:
21968513
DOI:
10.1093/hmg/ddr447
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Silverchair Information Systems
Loading ...
Support Center