TY - JOUR
T1 - α4 integrins regulate the proliferation/differentiation balance of multilineage hematopoietic progenitors in vivo
AU - Arroyo, Alicia G.
AU - Yang, Joy T.
AU - Rayburn, Helen
AU - Hynes, Richard O.
N1 - Funding Information:
We thank Valerie Evans for help in generation of chimeric mice, Daniela Taverna and Bernhard Bader for blood samples from chimeric mice, Herbert Haack and Steve Cornwall for help in mouse husbandry, Denise Crowley for histology assistance, and Colleen Leslie for manuscript editing. We are especially grateful to Len Zon, L. C. Wang, and A. A. Postigo for suggestions and encouragement. We also thank José-Carlos Gutiérrez-Ramos for the stromal cell line. This work was supported by a grant from the National Heart Lung and Blood Institute (PO1 HL41484) and by the Howard Hughes Medical Institute. A. G. A. was supported by fellowships from Human Frontiers Science Program and Merck.
PY - 1999/11
Y1 - 1999/11
N2 - We investigated roles of α4 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 α4 integrins. Although terminal differentiation of these progenitors is possible without α4 integrins, these receptors are essential to maintain normal hematopoiesis in fetal liver, spleen, and bone marrow microenvironments. Moreover, α4-deficient erythroid progenitors and pre-B cells neither transmigrate beneath the stroma nor expand properly in vitro. In contrast, α4-null cells migrate and differentiate efficiently into T lymphocytes within the thymus. In summary, α4 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.
AB - We investigated roles of α4 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 α4 integrins. Although terminal differentiation of these progenitors is possible without α4 integrins, these receptors are essential to maintain normal hematopoiesis in fetal liver, spleen, and bone marrow microenvironments. Moreover, α4-deficient erythroid progenitors and pre-B cells neither transmigrate beneath the stroma nor expand properly in vitro. In contrast, α4-null cells migrate and differentiate efficiently into T lymphocytes within the thymus. In summary, α4 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.
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U2 - 10.1016/S1074-7613(00)80131-4
DO - 10.1016/S1074-7613(00)80131-4
M3 - Article
C2 - 10591181
AN - SCOPUS:0033216389
SN - 1074-7613
VL - 11
SP - 555
EP - 566
JO - Immunity
JF - Immunity
IS - 5
ER -