A major role of TGF-beta1 in the homing capacities of murine hematopoietic stem cell/progenitors.
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.
Capron
Claude
C
Inserm U1009, Faculté de Médecine Paris XI, Institut Gustave Roussy, Villejuif, France.
Lacout
Catherine
C
Lécluse
Yann
Y
Jalbert
Valérie
V
Chagraoui
Hédia
H
Charrier
Sabine
S
Galy
Anne
A
Bennaceur-Griscelli
Annelise
A
Cramer-Bordé
Elisabeth
E
Vainchenker
William
W
D000818:Animals; D000831:Animals, Newborn; D001327:Autoimmune Diseases / Q000276:immunology* / Q000473:pathology; D015153:Blotting, Western; D001854:Bone Marrow Cells / Q000473:pathology; D019070:Cell Lineage; D002469:Cell Separation; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D004622:Embryo, Mammalian / Q000166:cytology / Q000378:metabolism; D005260:Female; D005333:Fetus; D005434:Flow Cytometry; D006410:Hematopoiesis; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D007249:Inflammation / Q000276:immunology* / Q000473:pathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D053773:Transforming Growth Factor beta1 / Q000502:physiology*
D016207:Cytokines; D012333:RNA, Messenger; D053773:Transforming Growth Factor beta1