HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 2005-0210v1 24/5/1359    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints/Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Bowles, K. M. Articles by Pedersen, R. A. Search for Related Content PubMed PubMed Citation Articles by Bowles, K. M. Articles by Pedersen, R. A.

EMBRYONIC STEM CELLS

HOXB4 Overexpression Promotes Hematopoietic Development by Human Embryonic Stem Cells

Department of Surgery, University of Cambridge, Cambridge Institute for Medical Research, Cambridge, United Kingdom

Key Words. Human embryonic stem cells • Hematopoiesis • Homeobox genes

Correspondence: K. M. Bowles, Department of Surgery, University of Cambridge, Cambridge Institute for Medical Research, Hills Road, Cambridge, CB2 2XY U.K. Telephone: +44 (0)1223-763237; Fax: +44 (0)1223-763350; e-mail: kmb43{at}cam.ac.uk

Received May 9, 2005; accepted for publication January 1, 2006.
Human embryonic stem cells (hESCs) are a potential source of hematopoietic cells for therapeutic transplantation and can provide a model for human hematopoiesis. Culture of hESCs on murine stromal layers or in stromal-free conditions as embryoid bodies results in low levels of hematopoietic cells. Here we demonstrate that overexpression of the transcription factor HOXB4 considerably augments hematopoietic development of hESCs. Stable HOXB4-expressing hESC clones were generated by lipofection and could be maintained in the undifferentiated state for prolonged passages. Moreover, differentiation of hESCs as embryoid bodies in serum-containing medium without the use of additional cytokines led to sequential expansion of first erythroid and then myeloid and monocytic progenitors from day 10 of culture. These cells retained the capacity to develop into formed blood elements during in vitro culture. Consistent with the development of committed hematopoietic cells, we observed the expression of transcription factors known to be critical for hematopoietic development. We thus demonstrate successful use of enforced gene expression to promote the differentiation of hESCs into a terminally differentiated tissue, thereby revealing an important role for HOXB4 in supporting their in vitro development along the hematopoietic pathway.

This article has been cited by other articles:

				S.-J. Lu, Q. Feng, J. S. Park, L. Vida, B.-S. Lee, M. Strausbauch, P. J. Wettstein, G. R. Honig, and R. Lanza Biologic properties and enucleation of red blood cells from human embryonic stem cells Blood, December 1, 2008; 112(12): 4475 - 4484. [Abstract] [Full Text] [PDF]

				C. Unger, E. Karner, A. Treschow, B. Stellan, U. Felldin, H. Concha, M. Wendel, O. Hovatta, A. Aints, L. Ahrlund-Richter, et al. Lentiviral-Mediated HoxB4 Expression in Human Embryonic Stem Cells Initiates Early Hematopoiesis in a Dose-Dependent Manner but Does Not Promote Myeloid Differentiation Stem Cells, October 1, 2008; 26(10): 2455 - 2466. [Abstract] [Full Text] [PDF]

				K.-M. Chan, S. Bonde, H. Klump, and N. Zavazava Hematopoiesis and immunity of HOXB4-transduced embryonic stem cell-derived hematopoietic progenitor cells Blood, March 15, 2008; 111(6): 2953 - 2961. [Abstract] [Full Text] [PDF]

				M. Bhatia Hematopoietic Development from Human Embryonic Stem Cells Hematology, January 1, 2007; 2007(1): 11 - 16. [Abstract] [Full Text] [PDF]