Hongmei Tang1, Song Chen, Haikun Wang, Hui Wu, Qingxian Lu, Daishu Han. 1. Department of Cell Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing, P.R. China.
Abstract
BACKGROUND: TAM receptors (Tyro3, Axl and Mer) are expressed in hematopoietic tissues. The roles of the three receptors in hematopoiesis are, however, largely unknown. We investigated the role of TAM receptors in regulating erythropoiesis. DESIGN AND METHODS: Single and double mutant mice for Axl and Mer were used in the study. Cellularity of bone marrow and spleen, hematologic parameters, flow cytometry analysis of erythroid cell maturation, erythropoietic response to acute hemolytic anemia, bone marrow transplantation and the expression of erythropoisis were analyzed to evaluate the function of Axl and Mer in erythropoiesis. RESULTS: Axl and Mer, but not Tyro3, were constitutively expressed in developing erythroid cells. Mice lacking Axl and Mer (Axl(-/-)Me(-/-)) had impaired erythropoiesis in bone marrow and expanded splenic erythropoiesis. We found an inhibition of differentiation at the transition from erythroid progenitors to proerythroblasts in Axl(-/-)Mer(-/-) mice. These mice exhibited a low rate of erythropoietic response to acute anemia induced by phenylhydrazine. Bone marrow transplantation studies showed that the impaired erythropoiesis in Axl(-/-)Mer(-/-) mice is erythroid cell-autonomous. TAM receptors may influence erythropoiesis through the regulation of GATA-1 erythropoietin receptor and EpoR expression in erythroid progenitors. Notably, mice lacking single Axl or Mer exhibited normal erythropoiesis in steady-state conditions. CONCLUSIONS: Axl and Mer play an important role in regulating erythropoiesis. This finding provides a novel insight into the mechanism of erythropoiesis.
BACKGROUND: TAM receptors (Tyro3, Axl and Mer) are expressed in hematopoietic tissues. The roles of the three receptors in hematopoiesis are, however, largely unknown. We investigated the role of TAM receptors in regulating erythropoiesis. DESIGN AND METHODS: Single and double mutant mice for Axl and Mer were used in the study. Cellularity of bone marrow and spleen, hematologic parameters, flow cytometry analysis of erythroid cell maturation, erythropoietic response to acute hemolytic anemia, bone marrow transplantation and the expression of erythropoisis were analyzed to evaluate the function of Axl and Mer in erythropoiesis. RESULTS:Axl and Mer, but not Tyro3, were constitutively expressed in developing erythroid cells. Mice lacking Axl and Mer (Axl(-/-)Me(-/-)) had impaired erythropoiesis in bone marrow and expanded splenic erythropoiesis. We found an inhibition of differentiation at the transition from erythroid progenitors to proerythroblasts in Axl(-/-)Mer(-/-) mice. These mice exhibited a low rate of erythropoietic response to acute anemia induced by phenylhydrazine. Bone marrow transplantation studies showed that the impaired erythropoiesis in Axl(-/-)Mer(-/-) mice is erythroid cell-autonomous. TAM receptors may influence erythropoiesis through the regulation of GATA-1 erythropoietin receptor and EpoR expression in erythroid progenitors. Notably, mice lacking single Axl or Mer exhibited normal erythropoiesis in steady-state conditions. CONCLUSIONS:Axl and Mer play an important role in regulating erythropoiesis. This finding provides a novel insight into the mechanism of erythropoiesis.
Authors: A Angelillo-Scherrer; P de Frutos; C Aparicio; E Melis; P Savi; F Lupu; J Arnout; M Dewerchin; M Hoylaerts; J Herbert; D Collen; B Dahlbäck; P Carmeliet Journal: Nat Med Date: 2001-02 Impact factor: 53.440
Authors: L Pevny; M C Simon; E Robertson; W H Klein; S F Tsai; V D'Agati; S H Orkin; F Costantini Journal: Nature Date: 1991-01-17 Impact factor: 49.962
Authors: A Neubauer; A Fiebeler; D K Graham; J P O'Bryan; C A Schmidt; P Barckow; S Serke; W Siegert; H R Snodgrass; D Huhn Journal: Blood Date: 1994-09-15 Impact factor: 22.113
Authors: Mona Saffarzadeh; Kristin Grunz; T Son Nguyen; Young K Lee; Maki Kitano; Sven Danckwardt; Carina D S Rodrigues; Hartmut Weiler; Sabine Reyda; Wolfram Ruf Journal: Blood Adv Date: 2020-11-24
Authors: Madeline G Huey; Katherine A Minson; H Shelton Earp; Deborah DeRyckere; Douglas K Graham Journal: Cancers (Basel) Date: 2016-11-08 Impact factor: 6.639