Alpha4 integrins regulate the proliferation/differentiation balance of multilineage hematopoietic progenitors in vivo.
We investigated roles of alpha4 integrins during hematopoiesis using mutant and chimeric mice. Yolk sac erythropoiesis and migration of hematopoietic progenitors to fetal liver, spleen, and bone marrow can occur without alpha4 integrins. Although terminal differentiation of these progenitors is possible without alpha4 integrins, these receptors are essential to maintain normal hematopoiesis in fetal liver, spleen, and bone marrow microenvironments. Moreover, alpha4-deficient erythroid progenitors and pre-B cells neither transmigrate beneath the stroma nor expand-properly in vitro. In contrast, alpha4-null cells migrate and differentiate efficiently into T lymphocytes within the thymus. In summary, alpha4 integrins are essential for normal development of all hematopoietic lineages in fetal liver, bone marrow, and spleen, likely by regulating the proliferation/differentiation balance of hematopoietic progenitors.
Arroyo
A G
AG
Howard Hughes Medical Institute, Center for Cancer Research, Cambridge, Massachusetts 02139, USA.
Yang
J T
JT
Rayburn
H
H
Hynes
R O
RO
D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000502:physiology*; D001402:B-Lymphocytes / Q000473:pathology; D001853:Bone Marrow / Q000196:embryology / Q000473:pathology; D002454:Cell Differentiation; D002455:Cell Division; D019070:Cell Lineage; D002465:Cell Movement; D004268:DNA-Binding Proteins / Q000172:deficiency; D015672:Erythroid Precursor Cells / Q000473:pathology; D004920:Erythropoiesis; D006410:Hematopoiesis / Q000502:physiology*; D006411:Hematopoiesis, Extramedullary; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D006413:Hematopoietic System / Q000196:embryology* / Q000473:pathology; D039441:Integrin alpha4; D008099:Liver / Q000196:embryology / Q000473:pathology; D008221:Lymphoid Tissue / Q000196:embryology* / Q000276:immunology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013154:Spleen / Q000196:embryology / Q000473:pathology; D013601:T-Lymphocytes / Q000166:cytology; D013950:Thymus Gland / Q000196:embryology; D015017:Yolk Sac / Q000473:pathology
D015703:Antigens, CD; D004268:DNA-Binding Proteins; C499308:Rag2 protein, mouse; C064655:V(D)J recombination activating protein 2; D039441:Integrin alpha4