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Blood, 1 December 2006, Vol. 108, No. 12, pp. 3707-3712.
Prepublished online as a Blood First Edition Paper on August 8, 2006; DOI 10.1182/blood-2006-02-003384.
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Submitted February 14, 2006
Accepted July 18, 2006
Smad5 is dispensable for adult murine hematopoiesis
Sofie Singbrant, Jennifer L Moody, Ulrika Blank, Goran Karlsson, Lieve Umans, An Zwijsen, and Stefan Karlsson*
Dept of Molecular Medicine & Gene Therapy, Lund Stem Cell Center, Lund University Hospital, Sweden
Interuniversity Institute for Biotechnology (VIB), University of Leuven, Belgium
* Corresponding author; email: stefan.karlsson{at}med.lu.se.
Smad5 is known to transduce intracellular signals from Bone Morphogenetic Proteins (BMPs), which belong to the Transforming Growth Factor- (TGF- ) superfamily and are involved in the regulation of hematopoiesis. Recent findings suggest that BMP4 stimulates proliferation of human primitive hematopoietic progenitors in vitro, while early progenitors from mice deficient in Smad5 display increased self-renewal capacity in murine embryonic hematopoiesis. Here, we evaluate the role of Smad5 in the regulation of hematopoietic stem cell (HSC) fate decisions in adult mice by using an inducible MxCre mediated conditional knockout model. Surprisingly, analysis of induced animals revealed unperturbed cell numbers and lineage distribution in peripheral blood (PB), bone marrow (BM) and spleen. Furthermore, phenotypic characterization of the stem cell compartment revealed normal numbers of primitive lin-Sca-1+c-Kit+ (LSK) cells in Smad5-/- BM. When transplanted in a competitive fashion into lethally irradiated primary and secondary recipients, Smad5 deficient BM cells competed normally with wild-type (wt) cells, were able to long-term reconstitute the hosts and displayed normal lineage distribution. Taken together, Smad5 deficient HSCs from adult mice show unaltered differentiation, proliferation, and repopulating capacity. Therefore, in contrast to its role in embryonic hematopoiesis, Smad5 is dispensable for hematopoiesis in the adult mouse.

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