The histone demethylase UTX regulates stem cell migration and hematopoiesis

被引：86

作者：

Thieme, Sebastian ^{[1
]}

Gyarfas, Tobias ^{[1
]}

Richter, Cornelia ^{[1
]}

Oezhan, Guenes ^{[2
]}

Fu, Jun ^{[2
]}

Alexopoulou, Dimitra ^{[2
]}

Muders, Michael H. ^{[3
]}

Michalk, Irene ^{[4
]}

Jakob, Christiane

Dahl, Andreas ^{[2
]}

Klink, Barbara ^{[5
]}

Bandola, Joanna ^{[1
]}

Bachmann, Michael ^{[4
]}

Schroeck, Evelin ^{[5
]}

Buchholz, Frank ^{[6
]}

Stewart, A. Francis ^{[2
,7
]}

Weidinger, Gilbert ^{[8
]}

Anastassiadis, Konstantinos ^{[2
,7
]}

Brenner, Sebastian ^{[1
,7
]}

机构：

[1] Univ Clin Carl Gustav Carus, Dept Pediat, D-01307 Dresden, Germany

[2] Tech Univ Dresden, BIOTEC, D-01062 Dresden, Germany

[3] Univ Clin Carl Gustav Carus, Dept Pathol, D-01307 Dresden, Germany

[4] Univ Clin Carl Gustav Carus, Inst Immunol, D-01307 Dresden, Germany

[5] Tech Univ Dresden, Fac Med Carl Gustav Carus, Inst Clin Genet, D-01062 Dresden, Germany

[6] Tech Univ Dresden, Univ Canc Ctr, D-01062 Dresden, Germany

[7] Tech Univ Dresden, Ctr Regenerat Therapies, D-01062 Dresden, Germany

[8] Univ Ulm, Inst Biochem & Mol Biol, D-89069 Ulm, Germany

来源：

BLOOD | 2013年 / 121卷 / 13期

关键词：

SITE-SPECIFIC RECOMBINASE; GENE; LEUKEMIA; MOUSE; DIFFERENTIATION; ERYTHROPOIESIS; EXPRESSION; JMJD3; MICE; ANNOTATION;

D O I：

10.1182/blood-2012-08-452003

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Regulated migration of hematopoietic stem cells is fundamental for hematopoiesis. The molecular mechanisms underlying stem cell trafficking are poorly defined. Based on a short hairpin RNA library and stromal cell-derived factor-1 (SDF-1) migration screening assay, we identified the histone 3 lysine 27 demethylase UTX (Kdm6a) as a novel regulator for hematopoietic cell migration. Using hematopoietic stem and progenitor cells from our conditional UTX knockout (KO) mice, we were able to confirm the regulatory function of UTX on cell migration. Moreover, adult female conditional UTX KO mice displayed myelodysplasia and splenic erythropoiesis, whereas UTX KO males showed no phenotype. During development, all UTX KO female and a portion of UTX KO male embryos developed a cardiac defect, cranioschisis, and died in utero. Therefore, UTY, the male homolog of UTX, can compensate for UTX in adults and partially during development. Additionally, we found that UTX knockdown in zebrafish significantly impairs SDF-1/CXCR4-dependent migration of primordial germ cells. Our data suggest that UTX is a critical regulator for stem cell migration and hematopoiesis.

引用

页码：2462 / 2473

页数：12

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