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EMBRYONIC STEM CELLS

Reduction of Shp-2 Expression by Small Interfering RNA Reduces Murine Embryonic Stem Cell-Derived In Vitro Hematopoietic Differentiation

Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, Indiana, USA

Key Words. Shp-2 • Embryonic stem cell • RNA interference • Small interfering RNA • Hemangioblast

Correspondence: Mervin C. Yoder, M.D., Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, 1044 West Walnut St., R4-402E, Indianapolis, Indiana 46202, USA. Telephone: 317-278-0598; Fax: 317-274-8928; e-mail: myoder{at}iupui.edu

Received June 16, 2005; accepted for publication October 28, 2005.
Shp-2 is a member of a small family of cytoplasmic Src homology 2 (SH2) domain-containing protein tyrosine phosphatases. Although Shp-2 has been shown to be necessary for hematopoiesis using a mouse model expressing a mutant residual protein (Shp-2^/), we used small interfering RNA (siRNA) to reduce Shp-2 expression and examined the consequences on embryonic stem cell (ESC)-derived hemangioblast, primitive, and definitive hematopoietic development. We found that at a concentration of 50 nM, Shp-2 siRNA effectively diminished Shp-2 expression in differentiating embryoid bodies. Hemangioblast, primitive, and definitive hematopoietic progenitor formation was decreased significantly after transfection with Shp-2 siRNA but not with scrambled siRNA. Because Shp-2 is involved in signals emanating from the basic fibroblast growth factor (bFGF) receptor, we asked whether Shp-2 functions in bFGF-mediated hemangioblast development. Reduction of Shp-2 expression using siRNA, but not scrambled siRNA, blocked the bFGF-induced increase in hemangioblast development. Using siRNA as an independent method of reducing Shp-2 function, in contrast to the mutant mouse model (Shp-2^/) previously used, we demonstrate that Shp-2 is required in hemangioblast, primitive, and definitive progenitor hematopoietic development and that Shp-2 is integrally necessary for bFGF-mediated hemangioblast production.

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