Methionine aminopeptidase 2 is required for HSC initiation and proliferation

Alvin C H Ma, Tsz K. Fung, Rachel H C Lin, Martin I S Chung, Dan Yang, Stephen C Ekker, Anskar Y H Leung

Research output: Contribution to journalArticle

15 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)5448-5457
Number of pages10
JournalBlood
Volume118
Issue number20
DOIs
StatePublished - Nov 17 2011

Fingerprint

Zebrafish
Hematopoiesis
Embryonic Structures
Severe Combined Immunodeficiency
Morpholinos
Calcium-Calmodulin-Dependent Protein Kinases
Aminopeptidases
Phosphorylation
Medical problems
Fetal Blood
Methionine
Ducts
Embryonic Development
Aorta
methionine aminopeptidase 2
fumagillin
Screening
Blood
Tissue
Derivatives

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

Ma, A. C. H., Fung, T. K., Lin, R. H. C., Chung, M. I. S., Yang, D., Ekker, S. C., & Leung, A. Y. H. (2011). Methionine aminopeptidase 2 is required for HSC initiation and proliferation. Blood, 118(20), 5448-5457. https://doi.org/10.1182/blood-2011-04-350173

Methionine aminopeptidase 2 is required for HSC initiation and proliferation. / Ma, Alvin C H; Fung, Tsz K.; Lin, Rachel H C; Chung, Martin I S; Yang, Dan; Ekker, Stephen C; Leung, Anskar Y H.

In: Blood, Vol. 118, No. 20, 17.11.2011, p. 5448-5457.

Research output: Contribution to journalArticle

Ma, ACH, Fung, TK, Lin, RHC, Chung, MIS, Yang, D, Ekker, SC & Leung, AYH 2011, 'Methionine aminopeptidase 2 is required for HSC initiation and proliferation', Blood, vol. 118, no. 20, pp. 5448-5457. https://doi.org/10.1182/blood-2011-04-350173
Ma, Alvin C H ; Fung, Tsz K. ; Lin, Rachel H C ; Chung, Martin I S ; Yang, Dan ; Ekker, Stephen C ; Leung, Anskar Y H. / Methionine aminopeptidase 2 is required for HSC initiation and proliferation. In: Blood. 2011 ; Vol. 118, No. 20. pp. 5448-5457.
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