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Article: Methionine aminopeptidase 2 is required for HSC initiation and proliferation
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TitleMethionine aminopeptidase 2 is required for HSC initiation and proliferation
 
AuthorsMa, ACH1
Fung, TK1
Lin, RHC1
Chung, MIS1
Yang, D3
Ekker, SC2
Leung, AYH1
 
Issue Date2011
 
PublisherAmerican Society of Hematology. The Journal's web site is located at http://bloodjournal.hematologylibrary.org/
 
CitationBlood, 2011, v. 118 n. 20, p. 5448-5457 [How to Cite?]
DOI: http://dx.doi.org/10.1182/blood-2011-04-350173
 
AbstractIn a chemical screening, we tested the antiangiogenic effects of fumagillin derivatives and identified fumagillin as an inhibitor of definitive hematopoiesis in zebrafish embryos. Fumagillin is known to target methionine aminopeptidase II (MetAP2), an enzyme whose function in hematopoiesis is unknown. We investigated the role of MetAP2 in hematopoiesis by using zebrafish embryo and human umbilical cord blood models. Zebrafish metap2 was expressed ubiquitously during early embryogenesis and later in the somitic region, the caudal hematopoietic tissue, and pronephric duct. metap2 was inhibited by morpholino and fumagillin treatment, resulting in increased mpo expression at 18 hours postfertilization and reduced c-myb expression along the ventral wall of dorsal aorta at 36 hours postfertilization. It also disrupted intersegmental vessels in Tg-(fli1:gfp) embryos without affecting development of major axial vasculatures. Inhibition of MetAP2 in CB CD34 + cells by fumagillin had no effect on overall clonogenic activity but significantly reduced their engraftment into immunodeficient nonobese diabetes/severe combined immunodeficiency mice. metap2 knockdown in zebrafish and inhibition by fumagillin in zebrafish and human CB CD34 + cells inhibited Calmodulin Kinase II activity and induced ERK phosphorylation. This study demonstrated a hithertoundescribed role of MetAP2 in definitive hematopoiesis and a possible link to non-canonical Wnt and ERK signaling. © 2011 by The American Society of Hematology.
 
ISSN0006-4971
2013 Impact Factor: 9.775
 
DOIhttp://dx.doi.org/10.1182/blood-2011-04-350173
 
PubMed Central IDPMC3342862
 
ISI Accession Number IDWOS:000297265400015
Funding AgencyGrant Number
General Research Fund (GRF)HKU 771110M
LKS Faculty of Medicine, The University of Hong Kong
Funding Information:

The work was supported by the General Research Fund (GRF; HKU 771110M) and an Innovative Collaborative Research Program from the LKS Faculty of Medicine, The University of Hong Kong.

 
ReferencesReferences in Scopus
 
GrantsA novel role of methionine aminopeptidase 2 (MetAP-2) in the regulation of hematopoietic stem cell during definitive hematopoiesis
 
DC FieldValue
dc.contributor.authorMa, ACH
 
dc.contributor.authorFung, TK
 
dc.contributor.authorLin, RHC
 
dc.contributor.authorChung, MIS
 
dc.contributor.authorYang, D
 
dc.contributor.authorEkker, SC
 
dc.contributor.authorLeung, AYH
 
dc.date.accessioned2012-03-27T08:56:06Z
 
dc.date.available2012-03-27T08:56:06Z
 
dc.date.issued2011
 
dc.description.abstractIn a chemical screening, we tested the antiangiogenic effects of fumagillin derivatives and identified fumagillin as an inhibitor of definitive hematopoiesis in zebrafish embryos. Fumagillin is known to target methionine aminopeptidase II (MetAP2), an enzyme whose function in hematopoiesis is unknown. We investigated the role of MetAP2 in hematopoiesis by using zebrafish embryo and human umbilical cord blood models. Zebrafish metap2 was expressed ubiquitously during early embryogenesis and later in the somitic region, the caudal hematopoietic tissue, and pronephric duct. metap2 was inhibited by morpholino and fumagillin treatment, resulting in increased mpo expression at 18 hours postfertilization and reduced c-myb expression along the ventral wall of dorsal aorta at 36 hours postfertilization. It also disrupted intersegmental vessels in Tg-(fli1:gfp) embryos without affecting development of major axial vasculatures. Inhibition of MetAP2 in CB CD34 + cells by fumagillin had no effect on overall clonogenic activity but significantly reduced their engraftment into immunodeficient nonobese diabetes/severe combined immunodeficiency mice. metap2 knockdown in zebrafish and inhibition by fumagillin in zebrafish and human CB CD34 + cells inhibited Calmodulin Kinase II activity and induced ERK phosphorylation. This study demonstrated a hithertoundescribed role of MetAP2 in definitive hematopoiesis and a possible link to non-canonical Wnt and ERK signaling. © 2011 by The American Society of Hematology.
 
dc.description.naturelink_to_OA_fulltext
 
dc.identifier.citationBlood, 2011, v. 118 n. 20, p. 5448-5457 [How to Cite?]
DOI: http://dx.doi.org/10.1182/blood-2011-04-350173
 
dc.identifier.doihttp://dx.doi.org/10.1182/blood-2011-04-350173
 
dc.identifier.eissn1528-0020
 
dc.identifier.epage5457
 
dc.identifier.hkuros198873
 
dc.identifier.hkuros223443
 
dc.identifier.isiWOS:000297265400015
Funding AgencyGrant Number
General Research Fund (GRF)HKU 771110M
LKS Faculty of Medicine, The University of Hong Kong
Funding Information:

The work was supported by the General Research Fund (GRF; HKU 771110M) and an Innovative Collaborative Research Program from the LKS Faculty of Medicine, The University of Hong Kong.

 
dc.identifier.issn0006-4971
2013 Impact Factor: 9.775
 
dc.identifier.issue20
 
dc.identifier.pmcidPMC3342862
 
dc.identifier.pmid21937698
 
dc.identifier.scopuseid_2-s2.0-81555214651
 
dc.identifier.spage5448
 
dc.identifier.urihttp://hdl.handle.net/10722/145873
 
dc.identifier.volume118
 
dc.languageeng
 
dc.publisherAmerican Society of Hematology. The Journal's web site is located at http://bloodjournal.hematologylibrary.org/
 
dc.publisher.placeUnited States
 
dc.relation.ispartofBlood
 
dc.relation.projectA novel role of methionine aminopeptidase 2 (MetAP-2) in the regulation of hematopoietic stem cell during definitive hematopoiesis
 
dc.relation.referencesReferences in Scopus
 
dc.rightsThis research was originally published in The Hematologist: ASH News and Reports. Author(s). Title. The Hematologist: ASH News and Reports. 2011; Vol 118, Issue 20: pp5448-pp5457. © the American Society of Hematology.
 
dc.subject.meshAminopeptidases - genetics - metabolism - physiology
 
dc.subject.meshAngiogenesis Inhibitors - pharmacology
 
dc.subject.meshGlycoproteins - genetics - physiology
 
dc.subject.meshHematopoietic Stem Cells - cytology - enzymology
 
dc.subject.meshMetalloendopeptidases - genetics - physiology
 
dc.titleMethionine aminopeptidase 2 is required for HSC initiation and proliferation
 
dc.typeArticle
 
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Author Affiliations
  1. The University of Hong Kong Li Ka Shing Faculty of Medicine
  2. Mayo Clinic
  3. The University of Hong Kong