Canonical Wnt signaling in megakaryocytes regulates proplatelet formation

被引：38

作者：

Macaulay, Iain C. ^{[1
]}

Thon, Jonathan N. ^{[2
]}

Tijssen, Marloes R. ^{[4
,5
]}

Steele, Brian M. ^{[1
]}

MacDonald, Bryan T. ^{[3
]}

Meade, Gerardene ^{[6
]}

Burns, Philippa ^{[4
,5
]}

Rendon, Augusto ^{[4
,5
,7
]}

Salunkhe, Vishal ^{[1
]}

Murphy, Ronan P. ^{[6
]}

Bennett, Cavan ^{[4
,5
]}

Watkins, Nicholas A. ^{[4
,5
]}

He, Xi ^{[3
]}

Fitzgerald, Desmond J. ^{[1
]}

Italiano, Joseph E., Jr. ^{[2
,8
]}

Maguire, Patricia B. ^{[1
]}

机构：

[1] Univ Coll Dublin, UCD Conway Inst, Sch Biomed & Biomol Sci, Dublin 4, Ireland

[2] Brigham & Womens Hosp, Div Hematol, Boston, MA 02115 USA

[3] Harvard Univ, Sch Med, Dept Neurol, FM Kirby Neurobiol Ctr,Childrens Hosp Boston, Boston, MA 02115 USA

[4] Univ Cambridge, Dept Haematol, Cambridge, England

[5] Natl Hlth Serv Blood & Transplant, Cambridge, England

[6] Dublin City Univ, Fac Sci & Hlth, Sch Hlth & Human Performance, Dublin 9, Ireland

[7] MRC Biostat Unit, Cambridge, England

[8] Childrens Hosp, Dept Surg, Vasc Biol Program, Boston, MA 02115 USA

来源：

BLOOD | 2013年 / 121卷 / 01期

基金：

爱尔兰科学基金会; 美国国家卫生研究院;

关键词：

WNT/BETA-CATENIN PATHWAY; HEMATOPOIETIC STEM-CELL; BETA-CATENIN; MOLECULAR-MECHANISMS; ENDOTHELIAL-CELLS; GENE-EXPRESSION; PROTEIN; MICE; THROMBOPOIESIS; MEGAKARYOPOIESIS;

D O I：

10.1182/blood-2012-03-416875

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Wnt signaling is involved in numerous aspects of vertebrate development and homeostasis, including the formation and function of blood cells. Here, we show that canonical and noncanonical Wnt signaling pathways are present and functional in megakaryocytes (MKs), with several Wnt effectors displaying MK-restricted expression. Using the CHRF288-11 cell line as a model for human MKs, the canonical Wnt3a signal was found to induce a time and dose-dependent increase in beta-catenin expression. beta-catenin accumulation was inhibited by the canonical antagonist dickkopf-1 (DKK1) and by the noncanonical agonist Wnt5a. Whole genome expression analysis demonstrated that Wnt3a and Wnt5a regulated distinct patterns of gene expression in MKs, and revealed a further interplay between canonical and noncanonical Wnt pathways. Fetal liver cells derived from low-density-lipoprotein receptor-related protein 6-deficient mice (LRP6(-/-)), generated dramatically reduced numbers of MKs in culture of lower ploidy (2N and 4N) than wild-type controls, implicating LRP6-dependent Wnt signaling in MK proliferation and maturation. Finally, in wild-type mature murine fetal liver-derived MKs, Wnt3a potently induced proplatelet formation, an effect that could be completely abrogated by DKK1. These data identify novel extrinsic regulators of proplatelet formation, and reveal a profound role for Wnt signaling in platelet production. (Blood. 2013; 121(1): 188-196)

引用

页码：188 / 196

页数：9

共 50 条

[1] Delivering new insight into the biology of megakaryopoiesis and thrombopoiesis [J].

Battinelli, Elisabeth M. ;

Hartwig, John H. ;

Italiano, Joseph E., Jr. .

CURRENT OPINION IN HEMATOLOGY, 2007, 14 (05) :419-426

[2] Outside-In Signalling Generated by a Constitutively Activated Integrin αIIbβ3 Impairs Proplatelet Formation in Human Megakaryocytes [J].

Bury, Loredana ;

Malara, Alessandro ;

Gresele, Paolo ;

Balduini, Alessandra .

PLOS ONE, 2012, 7 (04)

[3] β-catenin is dispensable for hematopoiesis and lymphopoiesis [J].

Cobas, M ;

Wilson, A ;

Ernst, B ;

Mancini, JC ;

MacDonald, HR ;

Kemler, R ;

Radtke, F .

JOURNAL OF EXPERIMENTAL MEDICINE, 2004, 199 (02) :221-229

[4] Wnt-expressing rat embryonic fibroblasts suppress Apo2L/TRAIL-induced apoptosis of human leukemia cells [J].

Doubravska, Lenka ;

Simova, Sarka ;

Cermak, Lukas ;

Valenta, Tomas ;

Korinek, Vladimir ;

Andera, Ladislav .

APOPTOSIS, 2008, 13 (04) :573-587

[5] Thrombopoietin signal transduction in purified murine megakaryocytes [J].

Drachman, JG ;

Sabath, DF ;

Fox, NE ;

Kaushansky, K .

BLOOD, 1997, 89 (02) :483-492

[6] lumi:: a pipeline for processing Illumina microarray [J].

Du, Pan ;

Kibbe, Warren A. ;

Lin, Simon M. .

BIOINFORMATICS, 2008, 24 (13) :1547-1548

[7] Wnt-3a and Dickkopf-1 stimulate neurite outgrowth in Ewing tumor cells via a Frizzled3-and c-Jun n-terminal kinase-dependent mechanism [J].

Endo, Yoshimi ;

Beauchamp, Elspeth ;

Woods, David ;

Taylor, William G. ;

Toretsky, Jeffrey A. ;

Uren, Aykut ;

Rubin, Jeffrey S. .

MOLECULAR AND CELLULAR BIOLOGY, 2008, 28 (07) :2368-2379

[8]

FUGMAN DA, 1990, BLOOD, V75, P1252

[9] Comparative, genome-scale transcriptional analysis of CHRF-288-11 and primary human megakaryocytic cell cultures provides novel insights into lineage-specific differentiation [J].

Fuhrken, Peter G. ;

Chen, Chi ;

Miller, William A. ;

Papoutsakis, Eleftherios T. .

EXPERIMENTAL HEMATOLOGY, 2007, 35 (03) :476-489

[10] The role of parathyroid hormone and insulin-like growth factors in hematopoietic niches: Physiology and pharmacology [J].

Garrett, R. W. ;

Emerson, S. G. .

MOLECULAR AND CELLULAR ENDOCRINOLOGY, 2008, 288 (1-2) :6-10

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