Brief Report: Ectopic Expression of Nup98-HoxA10 Augments Erythroid Differentiation of Human Embryonic Stem Cells§

Authors


  • Disclosure of potential conflicts of interest is found at the end of this article.

  • Author contributions: J.J. and R.M.R.: conception and design, analysis and interpretation, manuscript writing; S.H.: collection of data; D.A., P.R., and K.H.: provision of study material; M.B.: conception and design, analysis and interpretation, manuscript writing. J.J. and R.M.R. contributed equally to this article.

  • §

    First published online in STEM CELLSEXPRESS February 15, 2011.

Abstract

Hox genes encode highly conserved transcription factors that have been implicated in hematopoietic development and self-renewal of hematopoietic stem cells (HSCs) and hematopoietic development. The potency of NUP98-HOXA10hd (NA10) on adult murine bone marrow HSC self-renewal prompted us to examine its effect on specification and proliferation of hematopoietic cells derived from human embryonic stem cells (hESCs). Here, we demonstrate that expression of NA10 in hESCs influences the hematopoietic differentiation program. The specific effect of NA10 is dependent on the developmental stage of hematopoietic emergence from hESCs. Overexpression of NA10 in either undifferentiated hESCs or early hemogenic precursors augmented the frequency of CD45 GlycophorinA+ cells and erythroid progenitors (blast-forming unit-erythrocyte). In contrast, targeted NA10 expression in primitive CD34+ cells committed to the hematopoietic lineage had no effect on erythropoietic capacity but instead increased hematopoietic progenitor proliferation. Our study reveals a novel neomorphic effect of NA10 in early human erythroid development from pluripotent stem cells. STEM Cells 2011;29:736–741

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