The p47 GTPase Lrg-47 (Irgm1) links host defense and hematopoietic stem cell proliferation

被引：101

作者：

Feng, Carl G. ^{[1
]}

Weksberg, David C. ^{[2
,3
]}

Taylor, Gregory A. ^{[4
,5
,6
,7
]}

Sher, Alan ^{[1
]}

Goodell, Margaret A. ^{[2
]}

机构：

[1] NIAID, NIH, Parasit Dis Lab, Immunobiol Sect, Bethesda, MD 20892 USA

[2] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA

[3] Baylor Coll Med, Stem Cells & Regenerat Med Ctr, Houston, TX 77030 USA

[4] Duke Univ, Med Ctr, Ctr Study Aging & Human Dev, Dept Med, Durham, NC 27710 USA

[5] Duke Univ, Med Ctr, Ctr Study Aging & Human Dev, Dept Mol Genet & Microbiol, Durham, NC 27710 USA

[6] Duke Univ, Med Ctr, Ctr Study Aging & Human Dev, Dept Immunol, Durham, NC 27710 USA

[7] VA Med Ctr, GRECC, Durham, NC 27710 USA

来源：

CELL STEM CELL | 2008年 / 2卷 / 01期

关键词：

D O I：

10.1016/j.stem.2007.10.007

中图分类号：

Q813 [细胞工程];

学科分类号：

摘要：

Hematopoietic stem cells (HSCs) are self-renewing bone marrow cells that give rise to all blood lineages and retain a remarkable capacity to proliferate in response to insult. Although some controls on HSC activation are known, little is understood about how this process is linked to natural signals. We report that the interferon-inducible GTPase Lrg-47 (Irgm1), previously shown to play a critical role in host defense, inhibits baseline HSC proliferation and is required for a normal HSC response to chemical and infectious stimuli. Overproliferating Lrg-47(-/-) HSCs are severely impaired in functional repopulation assays, and when challenged with hematopoietic ablation by 5-fluorouracil or infection with Mycobacterium avium, Lrg-47(-/-) mice fail to achieve the expected expansion response in stem and progenitor cell populations. Our results establish a link between the response to infection and HSC activation and demonstrate a novel function for a member of the p47 GTPase family.

引用

页码：83 / 89

页数：7

共 34 条

[1] Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls [J].

Burton, Paul R. ;

Clayton, David G. ;

Cardon, Lon R. ;

Craddock, Nick ;

Deloukas, Panos ;

Duncanson, Audrey ;

Kwiatkowski, Dominic P. ;

McCarthy, Mark I. ;

Ouwehand, Willem H. ;

Samani, Nilesh J. ;

Todd, John A. ;

Donnelly, Peter ;

Barrett, Jeffrey C. ;

Davison, Dan ;

Easton, Doug ;

Evans, David ;

Leung, Hin-Tak ;

Marchini, Jonathan L. ;

Morris, Andrew P. ;

Spencer, Chris C. A. ;

Tobin, Martin D. ;

Attwood, Antony P. ;

Boorman, James P. ;

Cant, Barbara ;

Everson, Ursula ;

Hussey, Judith M. ;

Jolley, Jennifer D. ;

Knight, Alexandra S. ;

Koch, Kerstin ;

Meech, Elizabeth ;

Nutland, Sarah ;

Prowse, Christopher V. ;

Stevens, Helen E. ;

Taylor, Niall C. ;

Walters, Graham R. ;

Walker, Neil M. ;

Watkins, Nicholas A. ;

Winzer, Thilo ;

Jones, Richard W. ;

McArdle, Wendy L. ;

Ring, Susan M. ;

Strachan, David P. ;

Pembrey, Marcus ;

Breen, Gerome ;

St Clair, David ;

Caesar, Sian ;

Gordon-Smith, Katherine ;

Jones, Lisa ;

Fraser, Christine ;

Green, Elain K. .

NATURE, 2007, 447 (7145) :661-678

[2] p47 GTPases regulate Toxoplasma gondii survival in activated macrophages [J].

Butcher, BA ;

Greene, RI ;

Henry, SC ;

Annecharico, KL ;

Weinberg, JB ;

Denkers, EY ;

Sher, A ;

Taylor, GA .

INFECTION AND IMMUNITY, 2005, 73 (06) :3278-3286

[3] Hematopoietic stem cells do not engraft with absolute efficiencies [J].

Camargo, FD ;

Chambers, SM ;

Drew, E ;

McNagny, KM ;

Goodell, MA .

BLOOD, 2006, 107 (02) :501-507

[4] Inactivation of LRG-47 and IRG-47 reveals a family of interferon γ-inducible genes with essential, pathogen-specific roles in resistance to infection [J].

Collazo, CM ;

Yap, GS ;

Sempowski, GD ;

Lusby, KC ;

Tessarollo, L ;

Woude, GFV ;

Sher, A ;

Taylor, GA .

JOURNAL OF EXPERIMENTAL MEDICINE, 2001, 194 (02) :181-187

[5] Interferon γ and tumour necrosis factor α are overexpressed in bone marrow T lymphocytes from paediatric patients with aplastic anaemia [J].

Dufour, C ;

Corcione, A ;

Svahn, J ;

Haupt, R ;

Battilana, N ;

Pistoia, V .

BRITISH JOURNAL OF HAEMATOLOGY, 2001, 115 (04) :1023-1031

[6] Mice deficient in LRG-47 display increased susceptibility to mycobacterial infection associated with the induction of lymphopenia [J].

Feng, CG ;

Collazo-Custodio, CM ;

Eckhaus, M ;

Hieny, S ;

Belkaid, Y ;

Elkins, K ;

Jankovic, D ;

Taylor, GA ;

Sher, A .

JOURNAL OF IMMUNOLOGY, 2004, 172 (02) :1163-1168

[7] Dye efflux studies suggest that hematopoietic stem cells expressing low or undetectable levels of CD34 antigen exist in multiple species [J].

Goodell, MA ;

Rosenzweig, M ;

Kim, H ;

Marks, DF ;

DeMaria, M ;

Paradis, G ;

Grupp, SA ;

Sieff, CA ;

Mulligan, RC ;

Johnson, RP .

NATURE MEDICINE, 1997, 3 (12) :1337-1345

[8] Isolation and functional properties of murine hematopoietic stem cells that are replicating in vivo [J].

Goodell, MA ;

Brose, K ;

Paradis, G ;

Conner, AS ;

Mulligan, RC .

JOURNAL OF EXPERIMENTAL MEDICINE, 1996, 183 (04) :1797-1806

[9]

Haneline LS, 1998, BLOOD, V91, P4092

[10]

HARRISON DE, 1991, BLOOD, V78, P1237

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