Impaired functionality and homing of Fancg-deficient hematopoietic stem cells

被引：20

作者：

Barroca, Vilma ^{[1
,5
,6
,7
,8
]}

Mouthon, Marc Andre ^{[2
,6
,7
,8
]}

Lewandowski, Daniel ^{[3
,6
,7
,8
]}

de la Grange, Philippe Brunet ^{[4
,6
,7
,8
]}

Gauthier, Laurent Robert ^{[2
,6
,7
,8
]}

Pflumio, Francoise ^{[4
,6
,7
,8
]}

Boussin, Francois Dominique ^{[2
,6
,7
,8
]}

Arwert, Fre ^{[5
]}

Riou, Lydia ^{[1
,6
,7
,8
]}

Allemand, Isabelle ^{[1
,6
,7
,8
]}

Romeo, Paul Henri ^{[3
,6
,7
,8
]}

Fouchet, Pierre ^{[1
,6
,7
,8
]}

机构：

[1] Commissariat Energie Atom & Energies Alternat, Inst Radiobiol Cellulaire & Mol, Direct Sci Vivant, Lab Gametogenese Apoptose & Genotox, F-92265 Fontenay Aux Roses, France

[2] Commissariat Energie Atom & Energies Alternat, Inst Radiobiol Cellulaire & Mol, Direct Sci Vivant, Lab Radiopathol, F-92265 Fontenay Aux Roses, France

[3] Commissariat Energie Atom & Energies Alternat, Inst Radiobiol Cellulaire & Mol, Direct Sci Vivant, Lab Rech Reparat & Transcript Cellules Souches, F-92265 Fontenay Aux Roses, France

[4] Commissariat Energie Atom & Energies Alternat, Inst Radiobiol Cellulaire & Mol, Direct Sci Vivant, Lab Rech Cellules Souches Hematopoiet & Leucem, F-92265 Fontenay Aux Roses, France

[5] Vrije Univ, Univ Med Ctr, Dept Clin Genet, Amsterdam, Netherlands

[6] Inst Natl Sante & Rech Med, Unite 967, F-92265 Fontenay Aux Roses, France

[7] Univ Paris 07, F-92265 Paris, France

[8] Univ Paris 11, F-92265 Paris, France

来源：

HUMAN MOLECULAR GENETICS | 2012年 / 21卷 / 01期

关键词：

ANEMIA CORE COMPLEX; BONE-MARROW; OXIDATIVE STRESS; SELF-RENEWAL; MOUSE MODEL; DNA-DAMAGE; IN-VIVO; PROGENITOR CELLS; NULL MICE; LIFE-SPAN;

D O I：

10.1093/hmg/ddr447

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 longterm 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.

引用

页码：121 / 135

页数：15

共 53 条

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