Ape1 regulates hematopoietic differentiation of embryonic stem cells through its redox functional domain

Gang Ming Zou, Mei Hua Luo, April Reed, Mark Kelley, Mervin Yoder

Research output: Contribution to journalArticle

66 Citations (Scopus)

Abstract

Ape1 is a molecule with dual functions in DNA repair and redox regulation of transcription factors. In Ape1-deficient mice, embryos do not survive beyond embryonic day 9, indicating that this molecule is required for normal embryo development. Currently, direct evidence of the role of Ape1 in regulating hematopoiesis is lacking. We used the embryonic stem (ES) cell differentiation system and an siRNA approach to knockdown Ape1 gene expression to test the role of Ape1 in hematopoiesis. Hemangioblast development from ES cells was reduced 2- to 3-fold when Ape1 gene expression was knocked down by Ape1-specific siRNA, as was primitive and definitive hematopoiesis. Impaired hematopoiesis was not associated with increased apoptosis in siRNA-treated cells. To begin to explore the mechanism whereby Ape1 regulates hematopoiesis, we found that inhibition of the redox activity of Ape1 with E3330, a specific Ape1 redox inhibitor, but not Ape1 DNA repair activity, which was blocked using the small molecule methoxyamine, affected cytokine-mediated hemangioblast development in vitro. In summary, these data indicate Ape1 is required in normal embryonic hematopoiesis and that the redox function, but not the repair endonuclease activity, of Ape1 is critical in normal embryonic hematopoietic development.

Original languageEnglish
Pages (from-to)1917-1922
Number of pages6
JournalBlood
Volume109
Issue number5
DOIs
StatePublished - Mar 1 2007

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Hematopoiesis
Embryonic Stem Cells
Stem cells
Oxidation-Reduction
Small Interfering RNA
Repair
Hemangioblasts
Gene expression
Molecules
DNA Repair
Embryonic Development
Endonucleases
DNA
Gene Expression
Transcription Factors
Cells
Apoptosis
Cytokines
Cell Differentiation
Embryonic Structures

ASJC Scopus subject areas

  • Hematology

Cite this

Ape1 regulates hematopoietic differentiation of embryonic stem cells through its redox functional domain. / Zou, Gang Ming; Luo, Mei Hua; Reed, April; Kelley, Mark; Yoder, Mervin.

In: Blood, Vol. 109, No. 5, 01.03.2007, p. 1917-1922.

Research output: Contribution to journalArticle

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