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Blood, Vol. 92 No. 3 (August 1), 1998:
pp. 877-887
Overexpression of HOX11 Leads to the Immortalization of Embryonic
Precursors With Both Primitive and Definitive Hematopoietic Potential
Gordon Keller,
Charles Wall,
Andrew Z.C. Fong,
Teresa S. Hawley, and
Robert G. Hawley
From the National Jewish Medical and Research Center, Denver; the
Department of Immunology, University of Colorado Health Sciences
Center, Denver, CO; and the Oncology Gene Therapy Program, The Toronto
Hospital and Department of Medical Biophysics, University of Toronto,
Toronto, Ontario, Canada.
Primitive and definitive erythropoiesis represent distinct
hematopoietic programs that differ with respect to stage of
development, transcriptional control, and growth regulation. Although
these differences have been recognized for some time, the relationship of the two erythroid lineages to each other is not well established. We
have used a model system based on the hematopoietic development of
embryonic stem (ES) cells in culture to investigate the origins of the
earliest hematopoietic populations. Using ES cells transduced with a
retrovirus that overexpresses the HOX11 gene, we have
established factor-dependent hematopoietic cell lines that represent
novel stages of embryonic hematopoiesis. Analysis of three of these cell lines indicates that they differ with respect to cytokine responsiveness, cell surface markers, and developmental potential. Two
of the cell lines, EBHX1 and EBHX11, display the unique capacity to
generate both primitive and definitive erythroid progeny as defined by
morphology and expression of  H1 and major globin. The third line,
EBHX14, has definitive erythroid and myeloid potential, but is unable
to generate cells of the primitive erythroid lineage. Analysis of the
cytokine responsiveness of the two lines with primitive erythroid
potential has indicated that exposure to leukemia inhibitory factor
(LIF) results in the upregulation of H1 and a change in
cellular morphology to that of primitive erythrocytes. These findings
are the first demonstration of a clonal cell line with primitive and
definitive hematopoietic potential and support the interpretation that
these lineages may arise from a common precursor in embryonic life. In
addition, they suggest that LIF could play a role in the regulation of
primitive erythropoiesis.
© 1998 by The American Society of Hematology.
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