title: Smad5 is dispensable for adult murine hematopoiesis.
abstract: 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 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 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.
authors.affiliation: Lund University, BMC A12, 221 84 Lund, Sweden.
authors.forename: Sofie
authors.initials: S
authors.lastname: Singbrant
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Moody
authors.forename: Ulrika
authors.initials: U
authors.lastname: Blank
authors.forename: Goran
authors.initials: G
authors.lastname: Karlsson
authors.forename: Lieve
authors.initials: L
authors.lastname: Umans
authors.forename: An
authors.initials: A
authors.lastname: Zwijsen
authors.forename: Stefan
authors.initials: S
authors.lastname: Karlsson
mesh_terms: D000818:Animals; D000943:Antigens, Differentiation / Q000378:metabolism; D001853:Bone Marrow / Q000502:physiology; D002454:Cell Differentiation / Q000235:genetics / Q000528:radiation effects; D049109:Cell Proliferation / Q000528:radiation effects; D006410:Hematopoiesis / Q000235:genetics / Q000528:radiation effects; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000502:physiology*; D007958:Leukocyte Count; D051379:Mice; D018345:Mice, Knockout; D051902:Smad5 Protein / Q000172:deficiency / Q000378:metabolism*; D013154:Spleen / Q000166:cytology / Q000502:physiology; D033581:Stem Cell Transplantation / Q000379:methods; D018183:Transplantation Chimera / Q000502:physiology; D014916:Whole-Body Irradiation / Q000379:methods
chemical_list: D000943:Antigens, Differentiation; D051902:Smad5 Protein; C497798:Smad5 protein, mouse