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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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HEMATOPOIESIS

Smad5 is dispensable for adult murine hematopoiesis

Sofie Singbrant, Jennifer L. Moody, Ulrika Blank, Goran Karlsson, Lieve Umans, An Zwijsen, and Stefan Karlsson

From the Department of Molecular Medicine and Gene Therapy, Lund Stem Cell Center, Lund University Hospital, Lund, Sweden; and the Department of Developmental Biology, Flanders Interuniversity Institute for Biotechnology (VIB) and Laboratory of Molecular Biology (Celegen), University of Leuven, Belgium.

Smad5 is known to transduce intracellular signals from bone morphogenetic proteins (BMPs), which belong to the transforming growth factor-beta (TGF-beta) 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 the spleen. Furthermore, phenotypic characterization of the stem cell compartment revealed normal numbers of primitive linSca-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 provide long-term reconstitution for 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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