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Transforming growth factor-beta1 (TGF-beta1) is a pleiotropic cytokine with major in vitro effects on hematopoietic stem cells (HSCs) and lymphocyte development. Little is known about hematopoiesis from mice with constitutive TGF-beta1 inactivation largely because of important embryonic lethality and development of a lethal inflammatory disorder in TGF-beta1(-/-) pups, making these studies difficult. Here, we show that no sign of the inflammatory disorder was detectable in 8- to 10-day-old TGF-beta1(-/-) neonates as judged by both the number of T-activated and T-regulator cells in secondary lymphoid organs and the level of inflammatory cytokines in sera. After T-cell depletion, the inflammatory disease was not transplantable in recipient mice. Bone marrow cells from 8- to 10-day-old TGF-beta1(-/-) neonates showed strikingly impaired short- and long-term reconstitutive activity associated with a parallel decreased in vivo homing capacity of lineage negative (Lin(-)) cells. In addition an in vitro-reduced survival of immature progenitors (Lin(-) Kit(+) Sca(+)) was observed. Similar defects were found in liver cells from TGF-beta1(-/-) embryos on day 14 after vaginal plug. These data indicate that TGF-beta1 is a critical regulator for in vivo homeostasis of the HSCs, especially for their homing potential.

Original publication

DOI

10.1182/blood-2009-05-221093

Type

Journal article

Journal

Blood

Publication Date

26/08/2010

Volume

116

Pages

1244 - 1253

Keywords

Animals, Animals, Newborn, Autoimmune Diseases, Blotting, Western, Bone Marrow Cells, Cell Lineage, Cell Separation, Cells, Cultured, Cytokines, Embryo, Mammalian, Female, Fetus, Flow Cytometry, Hematopoiesis, Hematopoietic Stem Cell Transplantation, Hematopoietic Stem Cells, Inflammation, Male, Mice, Mice, Knockout, RNA, Messenger, Reverse Transcriptase Polymerase Chain Reaction, Transforming Growth Factor beta1