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Article: Methionine aminopeptidase 2 is required for HSC initiation and proliferation

TitleMethionine aminopeptidase 2 is required for HSC initiation and proliferation
Authors
Issue Date2011
PublisherAmerican Society of Hematology. The Journal's web site is located at http://bloodjournal.hematologylibrary.org/
Citation
Blood, 2011, v. 118 n. 20, p. 5448-5457 How to Cite?
Abstract
In 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.
Persistent Identifierhttp://hdl.handle.net/10722/145873
ISSN
2013 Impact Factor: 9.775
PubMed Central ID
ISI Accession Number ID
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.

References
Grants

 

Author Affiliations
  1. The University of Hong Kong Li Ka Shing Faculty of Medicine
  2. Mayo Clinic
  3. The University of Hong Kong
DC FieldValueLanguage
dc.contributor.authorMa, ACHen_HK
dc.contributor.authorFung, TKen_HK
dc.contributor.authorLin, RHCen_HK
dc.contributor.authorChung, MISen_HK
dc.contributor.authorYang, Den_HK
dc.contributor.authorEkker, SCen_HK
dc.contributor.authorLeung, AYHen_HK
dc.date.accessioned2012-03-27T08:56:06Z-
dc.date.available2012-03-27T08:56:06Z-
dc.date.issued2011en_HK
dc.identifier.citationBlood, 2011, v. 118 n. 20, p. 5448-5457en_HK
dc.identifier.issn0006-4971en_HK
dc.identifier.urihttp://hdl.handle.net/10722/145873-
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.en_HK
dc.languageengen_US
dc.publisherAmerican Society of Hematology. The Journal's web site is located at http://bloodjournal.hematologylibrary.org/en_HK
dc.relation.ispartofBlooden_HK
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 - physiologyen_HK
dc.subject.meshAngiogenesis Inhibitors - pharmacologyen_HK
dc.subject.meshGlycoproteins - genetics - physiologyen_HK
dc.subject.meshHematopoietic Stem Cells - cytology - enzymologyen_HK
dc.subject.meshMetalloendopeptidases - genetics - physiologyen_HK
dc.titleMethionine aminopeptidase 2 is required for HSC initiation and proliferationen_HK
dc.typeArticleen_HK
dc.identifier.emailYang, D:yangdan@hku.hken_HK
dc.identifier.emailLeung, AYH:ayhleung@hku.hken_HK
dc.identifier.authorityYang, D=rp00825en_HK
dc.identifier.authorityLeung, AYH=rp00265en_HK
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1182/blood-2011-04-350173en_HK
dc.identifier.pmid21937698en_HK
dc.identifier.pmcidPMC3342862-
dc.identifier.scopuseid_2-s2.0-81555214651en_HK
dc.identifier.hkuros198873en_US
dc.identifier.hkuros223443-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-81555214651&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume118en_HK
dc.identifier.issue20en_HK
dc.identifier.spage5448en_HK
dc.identifier.epage5457en_HK
dc.identifier.eissn1528-0020-
dc.identifier.isiWOS:000297265400015-
dc.publisher.placeUnited Statesen_HK
dc.relation.projectA novel role of methionine aminopeptidase 2 (MetAP-2) in the regulation of hematopoietic stem cell during definitive hematopoiesis-
dc.identifier.scopusauthoridMa, ACH=52664122100en_HK
dc.identifier.scopusauthoridFung, TK=7102715924en_HK
dc.identifier.scopusauthoridLin, RHC=16417180900en_HK
dc.identifier.scopusauthoridChung, MIS=25958659100en_HK
dc.identifier.scopusauthoridYang, D=7404800756en_HK
dc.identifier.scopusauthoridEkker, SC=7003541150en_HK
dc.identifier.scopusauthoridLeung, AYH=7403012668en_HK

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