共 51 条
Niche WNT5A regulates the actin cytoskeleton during regeneration of hematopoietic stem cells
被引:41
作者:

Schreck, Christina
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Tech Univ Munich, Klinikum Rechts Isar, Dept Internal Med 3, D-81675 Munich, Germany Tech Univ Munich, Klinikum Rechts Isar, Dept Internal Med 3, D-81675 Munich, Germany

Istvanffy, Rouzanna
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Tech Univ Munich, Klinikum Rechts Isar, Dept Internal Med 3, D-81675 Munich, Germany Tech Univ Munich, Klinikum Rechts Isar, Dept Internal Med 3, D-81675 Munich, Germany

Ziegenhain, Christoph
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Ludwig Maximilians Univ Munchen, Dept Biol 2, Anthropol & Human Genom, D-81377 Munich, Germany Tech Univ Munich, Klinikum Rechts Isar, Dept Internal Med 3, D-81675 Munich, Germany

Sippenauer, Theresa
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Tech Univ Munich, Klinikum Rechts Isar, Dept Internal Med 3, D-81675 Munich, Germany Tech Univ Munich, Klinikum Rechts Isar, Dept Internal Med 3, D-81675 Munich, Germany

Ruf, Franziska
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Tech Univ Munich, Klinikum Rechts Isar, Dept Internal Med 3, D-81675 Munich, Germany Tech Univ Munich, Klinikum Rechts Isar, Dept Internal Med 3, D-81675 Munich, Germany

Henkel, Lynette
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Tech Univ Munich, Dept Med Microbiol Immunol & Hyg, D-81675 Munich, Germany Tech Univ Munich, Klinikum Rechts Isar, Dept Internal Med 3, D-81675 Munich, Germany

Gaertner, Florian
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Ludwig Maximilians Univ Munchen, Dept Internal Med 1, D-81377 Munich, Germany Tech Univ Munich, Klinikum Rechts Isar, Dept Internal Med 3, D-81675 Munich, Germany

Vieth, Beate
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Ludwig Maximilians Univ Munchen, Dept Biol 2, Anthropol & Human Genom, D-81377 Munich, Germany Tech Univ Munich, Klinikum Rechts Isar, Dept Internal Med 3, D-81675 Munich, Germany

Florian, M. Carolina
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Univ Ulm, Inst Mol Med, D-89081 Ulm, Germany Tech Univ Munich, Klinikum Rechts Isar, Dept Internal Med 3, D-81675 Munich, Germany

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Taubenberger, Anna
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Tech Univ Dresden, Biotechnol Ctr, D-01307 Dresden, Germany Tech Univ Munich, Klinikum Rechts Isar, Dept Internal Med 3, D-81675 Munich, Germany

Prendergast, Aine
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机构:
German Canc Res Ctr, D-69120 Heidelberg, Germany
Heidelberg Inst Stem Cell Technol & Expt Med, D-69120 Heidelberg, Germany Tech Univ Munich, Klinikum Rechts Isar, Dept Internal Med 3, D-81675 Munich, Germany

Wagner, Alina
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Tech Univ Munich, Klinikum Rechts Isar, Dept Internal Med 3, D-81675 Munich, Germany Tech Univ Munich, Klinikum Rechts Isar, Dept Internal Med 3, D-81675 Munich, Germany

Pagel, Charlotta
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Tech Univ Munich, Klinikum Rechts Isar, Dept Internal Med 3, D-81675 Munich, Germany Tech Univ Munich, Klinikum Rechts Isar, Dept Internal Med 3, D-81675 Munich, Germany

Grziwok, Sandra
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Tech Univ Munich, Klinikum Rechts Isar, Dept Internal Med 3, D-81675 Munich, Germany Tech Univ Munich, Klinikum Rechts Isar, Dept Internal Med 3, D-81675 Munich, Germany

Goetze, Katharina S.
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Tech Univ Munich, Klinikum Rechts Isar, Dept Internal Med 3, D-81675 Munich, Germany
DKFZ, German Canc Consortium, D-69120 Heidelberg, Germany Tech Univ Munich, Klinikum Rechts Isar, Dept Internal Med 3, D-81675 Munich, Germany

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Dean, Douglas C.
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Univ Louisville, Hlth Sci Ctr, James Brown Canc Ctr, Mol Targets Program, Louisville, KY 40202 USA Tech Univ Munich, Klinikum Rechts Isar, Dept Internal Med 3, D-81675 Munich, Germany

Massberg, Steffen
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Ludwig Maximilians Univ Munchen, Dept Internal Med 1, D-81377 Munich, Germany Tech Univ Munich, Klinikum Rechts Isar, Dept Internal Med 3, D-81675 Munich, Germany

Essers, Marieke
论文数: 0 引用数: 0
h-index: 0
机构:
German Canc Res Ctr, D-69120 Heidelberg, Germany
Heidelberg Inst Stem Cell Technol & Expt Med, D-69120 Heidelberg, Germany Tech Univ Munich, Klinikum Rechts Isar, Dept Internal Med 3, D-81675 Munich, Germany

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Geiger, Hartmut
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Univ Ulm, Inst Mol Med, D-89081 Ulm, Germany Tech Univ Munich, Klinikum Rechts Isar, Dept Internal Med 3, D-81675 Munich, Germany

Schiemann, Mathias
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Tech Univ Munich, Dept Med Microbiol Immunol & Hyg, D-81675 Munich, Germany Tech Univ Munich, Klinikum Rechts Isar, Dept Internal Med 3, D-81675 Munich, Germany

Peschel, Christian
论文数: 0 引用数: 0
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Tech Univ Munich, Klinikum Rechts Isar, Dept Internal Med 3, D-81675 Munich, Germany
DKFZ, German Canc Consortium, D-69120 Heidelberg, Germany Tech Univ Munich, Klinikum Rechts Isar, Dept Internal Med 3, D-81675 Munich, Germany

Enard, Wolfgang
论文数: 0 引用数: 0
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Ludwig Maximilians Univ Munchen, Dept Biol 2, Anthropol & Human Genom, D-81377 Munich, Germany Tech Univ Munich, Klinikum Rechts Isar, Dept Internal Med 3, D-81675 Munich, Germany

Oostendorp, Robert A. J.
论文数: 0 引用数: 0
h-index: 0
机构:
Tech Univ Munich, Klinikum Rechts Isar, Dept Internal Med 3, D-81675 Munich, Germany Tech Univ Munich, Klinikum Rechts Isar, Dept Internal Med 3, D-81675 Munich, Germany
机构:
[1] Tech Univ Munich, Klinikum Rechts Isar, Dept Internal Med 3, D-81675 Munich, Germany
[2] Tech Univ Munich, Dept Med Microbiol Immunol & Hyg, D-81675 Munich, Germany
[3] Ludwig Maximilians Univ Munchen, Dept Biol 2, Anthropol & Human Genom, D-81377 Munich, Germany
[4] Ludwig Maximilians Univ Munchen, Dept Internal Med 1, D-81377 Munich, Germany
[5] Univ Ulm, Inst Mol Med, D-89081 Ulm, Germany
[6] Tech Univ Dresden, Inst Immunol, Regenerat Hematopoiesis & Anim Models Hematopoies, D-01309 Dresden, Germany
[7] Tech Univ Dresden, Biotechnol Ctr, D-01307 Dresden, Germany
[8] German Canc Res Ctr, D-69120 Heidelberg, Germany
[9] Heidelberg Inst Stem Cell Technol & Expt Med, D-69120 Heidelberg, Germany
[10] DKFZ, German Canc Consortium, D-69120 Heidelberg, Germany
[11] Univ Louisville, Hlth Sci Ctr, James Brown Canc Ctr, Mol Targets Program, Louisville, KY 40202 USA
关键词:
P21-ACTIVATED KINASE;
PROLIFERATION;
REPOPULATION;
MIGRATION;
BCR/ABL;
IMPAIRS;
POLYMERIZATION;
MAINTENANCE;
SIGNALS;
PATHWAY;
D O I:
10.1084/jem.20151414
中图分类号:
R392 [医学免疫学];
Q939.91 [免疫学];
学科分类号:
100102 ;
摘要:
Here, we show that the Wnt5a-haploinsufficient niche regenerates dysfunctional HSCs, which do not successfully engraft in secondary recipients. RNA sequencing of the regenerated donor Lin(-)SCA-1(+) KIT+ (LSK) cells shows dysregulated expression of ZEB1-associated genes involved in the small GTPase-dependent actin polymerization pathway. Misexpression of DOCK2, WAVE2, and activation of CDC42 results in apolar F-actin localization, leading to defects in adhesion, migration and homing of HSCs regenerated in a Wnt5a-haploinsufficient microenvironment. Moreover, these cells show increased differentiation in vitro, with rapid loss of HSC-enriched LSK cells. Our study further shows that the Wnt5a-haploinsufficient environment similarly affects BCR-ABLp(185) leukemia-initiating cells, which fail to generate leukemia in 42% of the studied recipients, or to transfer leukemia to secondary hosts. Thus, we show that WNT5A in the bone marrow niche is required to regenerate HSCs and leukemic cells with functional ability to rearrange the actin cytoskeleton and engraft successfully.
引用
收藏
页码:165 / 181
页数:17
相关论文
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Cincinnati Childrens Hosp, Cincinnati Childrens Res Fdn, Div Expt Hematol, Med Ctr, Cincinnati, OH USA Cincinnati Childrens Hosp, Cincinnati Childrens Res Fdn, Div Expt Hematol, Med Ctr, Cincinnati, OH USA

Dunn, Susan K.
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Cincinnati, Coll Med, Hoxworth Blood Ctr, Cincinnati, OH USA Cincinnati Childrens Hosp, Cincinnati Childrens Res Fdn, Div Expt Hematol, Med Ctr, Cincinnati, OH USA

Kuenzi, Ashley M.
论文数: 0 引用数: 0
h-index: 0
机构:
Cincinnati Childrens Hosp, Cincinnati Childrens Res Fdn, Div Expt Hematol, Med Ctr, Cincinnati, OH USA Cincinnati Childrens Hosp, Cincinnati Childrens Res Fdn, Div Expt Hematol, Med Ctr, Cincinnati, OH USA

Arnett, Jorden L.
论文数: 0 引用数: 0
h-index: 0
机构:
Cincinnati Childrens Hosp, Cincinnati Childrens Res Fdn, Div Expt Hematol, Med Ctr, Cincinnati, OH USA Cincinnati Childrens Hosp, Cincinnati Childrens Res Fdn, Div Expt Hematol, Med Ctr, Cincinnati, OH USA

Santho, Rebecca A.
论文数: 0 引用数: 0
h-index: 0
机构:
Cincinnati Childrens Hosp, Cincinnati Childrens Res Fdn, Div Expt Hematol, Med Ctr, Cincinnati, OH USA Cincinnati Childrens Hosp, Cincinnati Childrens Res Fdn, Div Expt Hematol, Med Ctr, Cincinnati, OH USA

Agirre, Xabier
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Navarra, Dept Hematol, Clin Univ Navarra, E-31080 Pamplona, Spain
Univ Navarra, Clin Univ Navarra, Fdn Appl Med Res, Area Cell Therapy, E-31080 Pamplona, Spain Cincinnati Childrens Hosp, Cincinnati Childrens Res Fdn, Div Expt Hematol, Med Ctr, Cincinnati, OH USA

Perentesis, John P.
论文数: 0 引用数: 0
h-index: 0
机构:
Cincinnati Childrens Hosp, Div Oncol, Med Ctr, Cincinnati, OH USA Cincinnati Childrens Hosp, Cincinnati Childrens Res Fdn, Div Expt Hematol, Med Ctr, Cincinnati, OH USA

Deininger, Michael W.
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Utah, Huntsman Canc Inst, Div Hematol & Hematol Malignancies, Salt Lake City, UT USA Cincinnati Childrens Hosp, Cincinnati Childrens Res Fdn, Div Expt Hematol, Med Ctr, Cincinnati, OH USA

Zheng, Yi
论文数: 0 引用数: 0
h-index: 0
机构:
Cincinnati Childrens Hosp, Cincinnati Childrens Res Fdn, Div Expt Hematol, Med Ctr, Cincinnati, OH USA Cincinnati Childrens Hosp, Cincinnati Childrens Res Fdn, Div Expt Hematol, Med Ctr, Cincinnati, OH USA

Bustelo, Xose R.
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Salamanca, Ctr Invest Canc, E-37008 Salamanca, Spain Cincinnati Childrens Hosp, Cincinnati Childrens Res Fdn, Div Expt Hematol, Med Ctr, Cincinnati, OH USA

Williams, David A.
论文数: 0 引用数: 0
h-index: 0
机构:
Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Pediat Hematol Oncol,Childrens Hosp Boston, Boston, MA 02115 USA
Harvard Univ, Sch Med, Harvard Stem Cell Inst, Boston, MA 02115 USA Cincinnati Childrens Hosp, Cincinnati Childrens Res Fdn, Div Expt Hematol, Med Ctr, Cincinnati, OH USA

Cancelas, Jose A.
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Cincinnati Childrens Hosp, Cincinnati Childrens Res Fdn, Div Expt Hematol, Med Ctr, Cincinnati, OH USA
Univ Cincinnati, Coll Med, Hoxworth Blood Ctr, Cincinnati, OH USA Cincinnati Childrens Hosp, Cincinnati Childrens Res Fdn, Div Expt Hematol, Med Ctr, Cincinnati, OH USA
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Chasseriau, J.
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Univ Poitiers, CNRS, Inst Phys & Biol Cellulaires, UMR 6187,Fac Sci, F-86021 Poitiers, France Univ Poitiers, CNRS, Inst Phys & Biol Cellulaires, UMR 6187,Fac Sci, F-86021 Poitiers, France

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Univ Poitiers, CNRS, Inst Phys & Biol Cellulaires, UMR 6187,Fac Sci, F-86021 Poitiers, France Univ Poitiers, CNRS, Inst Phys & Biol Cellulaires, UMR 6187,Fac Sci, F-86021 Poitiers, France

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CHU Poitiers, LGCM, Poitiers, France Univ Poitiers, CNRS, Inst Phys & Biol Cellulaires, UMR 6187,Fac Sci, F-86021 Poitiers, France

Kitzis, A.
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Poitiers, CNRS, Inst Phys & Biol Cellulaires, UMR 6187,Fac Sci, F-86021 Poitiers, France
CHU Poitiers, LGCM, Poitiers, France Univ Poitiers, CNRS, Inst Phys & Biol Cellulaires, UMR 6187,Fac Sci, F-86021 Poitiers, France

Constantin, B.
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Univ Poitiers, CNRS, Inst Phys & Biol Cellulaires, UMR 6187,Fac Sci, F-86021 Poitiers, France Univ Poitiers, CNRS, Inst Phys & Biol Cellulaires, UMR 6187,Fac Sci, F-86021 Poitiers, France

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h-index: 0
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Univ Poitiers, CNRS, Inst Phys & Biol Cellulaires, UMR 6187,Fac Sci, F-86021 Poitiers, France
CHU Poitiers, LGCM, Poitiers, France Univ Poitiers, CNRS, Inst Phys & Biol Cellulaires, UMR 6187,Fac Sci, F-86021 Poitiers, France
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Karolinska Inst, Sect Receptor Biol & Signaling, Dept Physiol & Pharmacol, S-17177 Stockholm, Sweden Karolinska Inst, Sect Receptor Biol & Signaling, Dept Physiol & Pharmacol, S-17177 Stockholm, Sweden

Petersen, J.
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h-index: 0
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Karolinska Inst, Sect Receptor Biol & Signaling, Dept Physiol & Pharmacol, S-17177 Stockholm, Sweden Karolinska Inst, Sect Receptor Biol & Signaling, Dept Physiol & Pharmacol, S-17177 Stockholm, Sweden

Schulte, G.
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Karolinska Inst, Sect Receptor Biol & Signaling, Dept Physiol & Pharmacol, S-17177 Stockholm, Sweden Karolinska Inst, Sect Receptor Biol & Signaling, Dept Physiol & Pharmacol, S-17177 Stockholm, Sweden