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Blood, 1 June 2002, Vol. 99, No. 11, pp. 3939-3946
HEMATOPOIESIS
Hematopoietic progenitor/stem cells immortalized by
Lhx2 generate functional hematopoietic cells in
vivo
Perpétua Pinto do Ó,
Karin Richter, and
Leif Carlsson
From the Department of Molecular Biology, Umeå
University, Sweden.
Hematopoietic stem cells (HSCs) are unique in their capacity to
maintain blood formation following transplantation into
immunocompromised hosts. Expansion of HSCs in vitro is therefore
important for many clinical applications but has met with limited
success because the mechanisms regulating the self-renewal process are
poorly defined. We have previously shown that expression of the
LIM-homeobox gene Lhx2 in hematopoietic progenitor
cells derived from embryonic stem cells differentiated in vitro
generates immortalized multipotent hematopoietic progenitor cell lines.
However, HSCs of early embryonic origin, including those derived from
differentiated embryonic stem cells, are inefficient in engrafting
adult recipients upon transplantation. To address whether
Lhx2 can immortalize hematopoietic progenitor/stem cells
that can engraft adult recipients, we expressed Lhx2 in
hematopoietic progenitor/stem cells derived from adult bone marrow.
This approach allowed for the generation of immortalized growth
factor-dependent hematopoietic progenitor/stem cell lines that can
generate erythroid, myeloid, and lymphoid cells upon transplantation
into lethally irradiated mice. When transplanted into stem
cell-deficient mice, these cell lines can generate a significant
proportion of circulating erythrocytes in primary, secondary, and
tertiary recipients for at least 18 months. Thus, Lhx2
immortalizes multipotent hematopoietic progenitor/stem cells that can
generate functional progeny following transplantation into lethally
irradiated hosts and can long-term repopulate stem cell-deficient hosts.
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