The Experts below are selected from a list of 246 Experts worldwide ranked by ideXlab platform

Merav Socolovsky - One of the best experts on this subject based on the ideXlab platform.

  • Suppression of Fas-FasL coexpression by Erythropoietin mediates erythroblast expansion during the erythropoietic stress response in vivo
    Blood, 2006
    Co-Authors: Ying Liu, Ramona Pop, Cameron Sadegh, Volker H Haase, Carlo Brugnara, Merav Socolovsky
    Abstract:

    Erythropoietin (Epo) is the principal regulator of the erythropoietic response to hypoxic stress, through its receptor, EpoR. The EpoR signals mediating the stress response are largely unknown, and the spectrum of progenitors that are stress responsive is not fully defined. Here, we used flow cytometry to identify stress-responsive Ter119+CD71highFSChigh early erythroblast subsets in vivo. In the mouse spleen, an erythropoietic reserve organ, early erythroblasts were present at lower frequencies and were undergoing higher rates of apoptosis than equivalent cells in bone marrow. A high proportion of splenic early erythroblasts coexpressed the death receptor Fas, and its ligand, FasL. Fas-positive early erythroblasts were significantly more likely to coexpress annexin V than equivalent, Fas-negative cells, suggesting that Fas mediates early erythroblast apoptosis in vivo. We examined several mouse models of erythropoietic stress, including erythrocytosis and beta-thalassemia. We found a dramatic increase in the frequency of splenic early erythroblasts that correlated with down-regulation of Fas and FasL from their cell surface. Further, a single injection of Epo specifically suppressed early erythroblast Fas and FasL mRNA and cell-surface expression. Therefore, Fas and FasL are negative regulators of erythropoiesis. Epo-mediated suppression of erythroblast Fas and FasL is a novel stress response pathway that facilitates erythroblast expansion in vivo.

  • ineffective erythropoiesis in stat5a 5b mice due to decreased survival of early erythroblasts
    Blood, 2001
    Co-Authors: Merav Socolovsky, Volker H Haase, Carlo Brugnara, Mark D. Fleming, Harvey F. Lodish
    Abstract:

    Erythropoietin (Epo) controls red cell production in the basal state and during stress. Epo binding to its receptor, EpoR, on erythroid progenitors leads to rapid activation of the transcription factor Stat5. Previously, fetal anemia and increased apoptosis of fetal liver erythroid progenitors were found in Stat5a−/−5b−/− mice. However, the role of Stat5 in adult erythropoiesis was not clear. The present study shows that some adult Stat5a−/−5b−/− mice have a near-normal hematocrit but are deficient in generating high erythropoietic rates in response to stress. Further, many adult Stat5a−/−5b−/− mice have persistent anemia despite a marked compensatory expansion in their erythropoietic tissue. Analysis of erythroblast maturation in Stat5a−/−5b−/− hematopoietic tissue shows a dramatic increase in early erythroblast numbers, but these fail to progress in differentiation. Decreased expression of bcl-xLand increased apoptosis in Stat5a−/−5b−/−early erythroblasts correlate with the degree of anemia. Hence, Stat5 controls a rate-determining step regulating early erythroblast survival.

  • Ineffective erythropoiesis in Stat5a(-/-)5b(-/-) mice due to decreased survival of early erythroblasts.
    Blood, 2001
    Co-Authors: Merav Socolovsky, Volker H Haase, Carlo Brugnara, Mark D. Fleming, Harvey F. Lodish
    Abstract:

    Erythropoietin (Epo) controls red cell production in the basal state and during stress. Epo binding to its receptor, EpoR, on erythroid progenitors leads to rapid activation of the transcription factor Stat5. Previously, fetal anemia and increased apoptosis of fetal liver erythroid progenitors were found in Stat5a−/−5b−/− mice. However, the role of Stat5 in adult erythropoiesis was not clear. The present study shows that some adult Stat5a−/−5b−/− mice have a near-normal hematocrit but are deficient in generating high erythropoietic rates in response to stress. Further, many adult Stat5a−/−5b−/− mice have persistent anemia despite a marked compensatory expansion in their erythropoietic tissue. Analysis of erythroblast maturation in Stat5a−/−5b−/− hematopoietic tissue shows a dramatic increase in early erythroblast numbers, but these fail to progress in differentiation. Decreased expression of bcl-xLand increased apoptosis in Stat5a−/−5b−/−early erythroblasts correlate with the degree of anemia. Hence, Stat5 controls a rate-determining step regulating early erythroblast survival.

  • fetal anemia and apoptosis of red cell progenitors in stat5a 5b mice a direct role for stat5 in bcl xl induction
    Cell, 1999
    Co-Authors: Merav Socolovsky, Carlo Brugnara, Amy Fallon, Stream Wang, Harvey F. Lodish
    Abstract:

    Abstract The Erythropoietin receptor (EpoR) is essential for production of red blood cells; a principal function of EpoR is to rescue committed erythroid progenitors from apoptosis. Stat5 is rapidly activated following EpoR stimulation, but its function in erythropoiesis has been unclear since adult Stat5a −/− 5b −/− mice have normal steady-state hematocrit. Here we show that Stat5 is essential for the high erythropoietic rate during fetal development. Stat5a −/− 5b −/− embryos are severely anemic; erythroid progenitors are present in low numbers, show higher levels of apoptosis, and are less responsive to Epo. These findings are explained by a crucial role for Stat5 in EpoR's antiapoptotic signaling: it mediates the immediate-early induction of Bcl-X L in erythroid cells through direct binding to the Bcl-X promoter.

Harvey F. Lodish - One of the best experts on this subject based on the ideXlab platform.

  • ineffective erythropoiesis in stat5a 5b mice due to decreased survival of early erythroblasts
    Blood, 2001
    Co-Authors: Merav Socolovsky, Volker H Haase, Carlo Brugnara, Mark D. Fleming, Harvey F. Lodish
    Abstract:

    Erythropoietin (Epo) controls red cell production in the basal state and during stress. Epo binding to its receptor, EpoR, on erythroid progenitors leads to rapid activation of the transcription factor Stat5. Previously, fetal anemia and increased apoptosis of fetal liver erythroid progenitors were found in Stat5a−/−5b−/− mice. However, the role of Stat5 in adult erythropoiesis was not clear. The present study shows that some adult Stat5a−/−5b−/− mice have a near-normal hematocrit but are deficient in generating high erythropoietic rates in response to stress. Further, many adult Stat5a−/−5b−/− mice have persistent anemia despite a marked compensatory expansion in their erythropoietic tissue. Analysis of erythroblast maturation in Stat5a−/−5b−/− hematopoietic tissue shows a dramatic increase in early erythroblast numbers, but these fail to progress in differentiation. Decreased expression of bcl-xLand increased apoptosis in Stat5a−/−5b−/−early erythroblasts correlate with the degree of anemia. Hence, Stat5 controls a rate-determining step regulating early erythroblast survival.

  • Ineffective erythropoiesis in Stat5a(-/-)5b(-/-) mice due to decreased survival of early erythroblasts.
    Blood, 2001
    Co-Authors: Merav Socolovsky, Volker H Haase, Carlo Brugnara, Mark D. Fleming, Harvey F. Lodish
    Abstract:

    Erythropoietin (Epo) controls red cell production in the basal state and during stress. Epo binding to its receptor, EpoR, on erythroid progenitors leads to rapid activation of the transcription factor Stat5. Previously, fetal anemia and increased apoptosis of fetal liver erythroid progenitors were found in Stat5a−/−5b−/− mice. However, the role of Stat5 in adult erythropoiesis was not clear. The present study shows that some adult Stat5a−/−5b−/− mice have a near-normal hematocrit but are deficient in generating high erythropoietic rates in response to stress. Further, many adult Stat5a−/−5b−/− mice have persistent anemia despite a marked compensatory expansion in their erythropoietic tissue. Analysis of erythroblast maturation in Stat5a−/−5b−/− hematopoietic tissue shows a dramatic increase in early erythroblast numbers, but these fail to progress in differentiation. Decreased expression of bcl-xLand increased apoptosis in Stat5a−/−5b−/−early erythroblasts correlate with the degree of anemia. Hence, Stat5 controls a rate-determining step regulating early erythroblast survival.

  • fetal anemia and apoptosis of red cell progenitors in stat5a 5b mice a direct role for stat5 in bcl xl induction
    Cell, 1999
    Co-Authors: Merav Socolovsky, Carlo Brugnara, Amy Fallon, Stream Wang, Harvey F. Lodish
    Abstract:

    Abstract The Erythropoietin receptor (EpoR) is essential for production of red blood cells; a principal function of EpoR is to rescue committed erythroid progenitors from apoptosis. Stat5 is rapidly activated following EpoR stimulation, but its function in erythropoiesis has been unclear since adult Stat5a −/− 5b −/− mice have normal steady-state hematocrit. Here we show that Stat5 is essential for the high erythropoietic rate during fetal development. Stat5a −/− 5b −/− embryos are severely anemic; erythroid progenitors are present in low numbers, show higher levels of apoptosis, and are less responsive to Epo. These findings are explained by a crucial role for Stat5 in EpoR's antiapoptotic signaling: it mediates the immediate-early induction of Bcl-X L in erythroid cells through direct binding to the Bcl-X promoter.

Carlo Brugnara - One of the best experts on this subject based on the ideXlab platform.

  • Suppression of Fas-FasL coexpression by Erythropoietin mediates erythroblast expansion during the erythropoietic stress response in vivo
    Blood, 2006
    Co-Authors: Ying Liu, Ramona Pop, Cameron Sadegh, Volker H Haase, Carlo Brugnara, Merav Socolovsky
    Abstract:

    Erythropoietin (Epo) is the principal regulator of the erythropoietic response to hypoxic stress, through its receptor, EpoR. The EpoR signals mediating the stress response are largely unknown, and the spectrum of progenitors that are stress responsive is not fully defined. Here, we used flow cytometry to identify stress-responsive Ter119+CD71highFSChigh early erythroblast subsets in vivo. In the mouse spleen, an erythropoietic reserve organ, early erythroblasts were present at lower frequencies and were undergoing higher rates of apoptosis than equivalent cells in bone marrow. A high proportion of splenic early erythroblasts coexpressed the death receptor Fas, and its ligand, FasL. Fas-positive early erythroblasts were significantly more likely to coexpress annexin V than equivalent, Fas-negative cells, suggesting that Fas mediates early erythroblast apoptosis in vivo. We examined several mouse models of erythropoietic stress, including erythrocytosis and beta-thalassemia. We found a dramatic increase in the frequency of splenic early erythroblasts that correlated with down-regulation of Fas and FasL from their cell surface. Further, a single injection of Epo specifically suppressed early erythroblast Fas and FasL mRNA and cell-surface expression. Therefore, Fas and FasL are negative regulators of erythropoiesis. Epo-mediated suppression of erythroblast Fas and FasL is a novel stress response pathway that facilitates erythroblast expansion in vivo.

  • ineffective erythropoiesis in stat5a 5b mice due to decreased survival of early erythroblasts
    Blood, 2001
    Co-Authors: Merav Socolovsky, Volker H Haase, Carlo Brugnara, Mark D. Fleming, Harvey F. Lodish
    Abstract:

    Erythropoietin (Epo) controls red cell production in the basal state and during stress. Epo binding to its receptor, EpoR, on erythroid progenitors leads to rapid activation of the transcription factor Stat5. Previously, fetal anemia and increased apoptosis of fetal liver erythroid progenitors were found in Stat5a−/−5b−/− mice. However, the role of Stat5 in adult erythropoiesis was not clear. The present study shows that some adult Stat5a−/−5b−/− mice have a near-normal hematocrit but are deficient in generating high erythropoietic rates in response to stress. Further, many adult Stat5a−/−5b−/− mice have persistent anemia despite a marked compensatory expansion in their erythropoietic tissue. Analysis of erythroblast maturation in Stat5a−/−5b−/− hematopoietic tissue shows a dramatic increase in early erythroblast numbers, but these fail to progress in differentiation. Decreased expression of bcl-xLand increased apoptosis in Stat5a−/−5b−/−early erythroblasts correlate with the degree of anemia. Hence, Stat5 controls a rate-determining step regulating early erythroblast survival.

  • Ineffective erythropoiesis in Stat5a(-/-)5b(-/-) mice due to decreased survival of early erythroblasts.
    Blood, 2001
    Co-Authors: Merav Socolovsky, Volker H Haase, Carlo Brugnara, Mark D. Fleming, Harvey F. Lodish
    Abstract:

    Erythropoietin (Epo) controls red cell production in the basal state and during stress. Epo binding to its receptor, EpoR, on erythroid progenitors leads to rapid activation of the transcription factor Stat5. Previously, fetal anemia and increased apoptosis of fetal liver erythroid progenitors were found in Stat5a−/−5b−/− mice. However, the role of Stat5 in adult erythropoiesis was not clear. The present study shows that some adult Stat5a−/−5b−/− mice have a near-normal hematocrit but are deficient in generating high erythropoietic rates in response to stress. Further, many adult Stat5a−/−5b−/− mice have persistent anemia despite a marked compensatory expansion in their erythropoietic tissue. Analysis of erythroblast maturation in Stat5a−/−5b−/− hematopoietic tissue shows a dramatic increase in early erythroblast numbers, but these fail to progress in differentiation. Decreased expression of bcl-xLand increased apoptosis in Stat5a−/−5b−/−early erythroblasts correlate with the degree of anemia. Hence, Stat5 controls a rate-determining step regulating early erythroblast survival.

  • fetal anemia and apoptosis of red cell progenitors in stat5a 5b mice a direct role for stat5 in bcl xl induction
    Cell, 1999
    Co-Authors: Merav Socolovsky, Carlo Brugnara, Amy Fallon, Stream Wang, Harvey F. Lodish
    Abstract:

    Abstract The Erythropoietin receptor (EpoR) is essential for production of red blood cells; a principal function of EpoR is to rescue committed erythroid progenitors from apoptosis. Stat5 is rapidly activated following EpoR stimulation, but its function in erythropoiesis has been unclear since adult Stat5a −/− 5b −/− mice have normal steady-state hematocrit. Here we show that Stat5 is essential for the high erythropoietic rate during fetal development. Stat5a −/− 5b −/− embryos are severely anemic; erythroid progenitors are present in low numbers, show higher levels of apoptosis, and are less responsive to Epo. These findings are explained by a crucial role for Stat5 in EpoR's antiapoptotic signaling: it mediates the immediate-early induction of Bcl-X L in erythroid cells through direct binding to the Bcl-X promoter.

Volker H Haase - One of the best experts on this subject based on the ideXlab platform.

  • Suppression of Fas-FasL coexpression by Erythropoietin mediates erythroblast expansion during the erythropoietic stress response in vivo
    Blood, 2006
    Co-Authors: Ying Liu, Ramona Pop, Cameron Sadegh, Volker H Haase, Carlo Brugnara, Merav Socolovsky
    Abstract:

    Erythropoietin (Epo) is the principal regulator of the erythropoietic response to hypoxic stress, through its receptor, EpoR. The EpoR signals mediating the stress response are largely unknown, and the spectrum of progenitors that are stress responsive is not fully defined. Here, we used flow cytometry to identify stress-responsive Ter119+CD71highFSChigh early erythroblast subsets in vivo. In the mouse spleen, an erythropoietic reserve organ, early erythroblasts were present at lower frequencies and were undergoing higher rates of apoptosis than equivalent cells in bone marrow. A high proportion of splenic early erythroblasts coexpressed the death receptor Fas, and its ligand, FasL. Fas-positive early erythroblasts were significantly more likely to coexpress annexin V than equivalent, Fas-negative cells, suggesting that Fas mediates early erythroblast apoptosis in vivo. We examined several mouse models of erythropoietic stress, including erythrocytosis and beta-thalassemia. We found a dramatic increase in the frequency of splenic early erythroblasts that correlated with down-regulation of Fas and FasL from their cell surface. Further, a single injection of Epo specifically suppressed early erythroblast Fas and FasL mRNA and cell-surface expression. Therefore, Fas and FasL are negative regulators of erythropoiesis. Epo-mediated suppression of erythroblast Fas and FasL is a novel stress response pathway that facilitates erythroblast expansion in vivo.

  • ineffective erythropoiesis in stat5a 5b mice due to decreased survival of early erythroblasts
    Blood, 2001
    Co-Authors: Merav Socolovsky, Volker H Haase, Carlo Brugnara, Mark D. Fleming, Harvey F. Lodish
    Abstract:

    Erythropoietin (Epo) controls red cell production in the basal state and during stress. Epo binding to its receptor, EpoR, on erythroid progenitors leads to rapid activation of the transcription factor Stat5. Previously, fetal anemia and increased apoptosis of fetal liver erythroid progenitors were found in Stat5a−/−5b−/− mice. However, the role of Stat5 in adult erythropoiesis was not clear. The present study shows that some adult Stat5a−/−5b−/− mice have a near-normal hematocrit but are deficient in generating high erythropoietic rates in response to stress. Further, many adult Stat5a−/−5b−/− mice have persistent anemia despite a marked compensatory expansion in their erythropoietic tissue. Analysis of erythroblast maturation in Stat5a−/−5b−/− hematopoietic tissue shows a dramatic increase in early erythroblast numbers, but these fail to progress in differentiation. Decreased expression of bcl-xLand increased apoptosis in Stat5a−/−5b−/−early erythroblasts correlate with the degree of anemia. Hence, Stat5 controls a rate-determining step regulating early erythroblast survival.

  • Ineffective erythropoiesis in Stat5a(-/-)5b(-/-) mice due to decreased survival of early erythroblasts.
    Blood, 2001
    Co-Authors: Merav Socolovsky, Volker H Haase, Carlo Brugnara, Mark D. Fleming, Harvey F. Lodish
    Abstract:

    Erythropoietin (Epo) controls red cell production in the basal state and during stress. Epo binding to its receptor, EpoR, on erythroid progenitors leads to rapid activation of the transcription factor Stat5. Previously, fetal anemia and increased apoptosis of fetal liver erythroid progenitors were found in Stat5a−/−5b−/− mice. However, the role of Stat5 in adult erythropoiesis was not clear. The present study shows that some adult Stat5a−/−5b−/− mice have a near-normal hematocrit but are deficient in generating high erythropoietic rates in response to stress. Further, many adult Stat5a−/−5b−/− mice have persistent anemia despite a marked compensatory expansion in their erythropoietic tissue. Analysis of erythroblast maturation in Stat5a−/−5b−/− hematopoietic tissue shows a dramatic increase in early erythroblast numbers, but these fail to progress in differentiation. Decreased expression of bcl-xLand increased apoptosis in Stat5a−/−5b−/−early erythroblasts correlate with the degree of anemia. Hence, Stat5 controls a rate-determining step regulating early erythroblast survival.

Mark D. Fleming - One of the best experts on this subject based on the ideXlab platform.

  • ineffective erythropoiesis in stat5a 5b mice due to decreased survival of early erythroblasts
    Blood, 2001
    Co-Authors: Merav Socolovsky, Volker H Haase, Carlo Brugnara, Mark D. Fleming, Harvey F. Lodish
    Abstract:

    Erythropoietin (Epo) controls red cell production in the basal state and during stress. Epo binding to its receptor, EpoR, on erythroid progenitors leads to rapid activation of the transcription factor Stat5. Previously, fetal anemia and increased apoptosis of fetal liver erythroid progenitors were found in Stat5a−/−5b−/− mice. However, the role of Stat5 in adult erythropoiesis was not clear. The present study shows that some adult Stat5a−/−5b−/− mice have a near-normal hematocrit but are deficient in generating high erythropoietic rates in response to stress. Further, many adult Stat5a−/−5b−/− mice have persistent anemia despite a marked compensatory expansion in their erythropoietic tissue. Analysis of erythroblast maturation in Stat5a−/−5b−/− hematopoietic tissue shows a dramatic increase in early erythroblast numbers, but these fail to progress in differentiation. Decreased expression of bcl-xLand increased apoptosis in Stat5a−/−5b−/−early erythroblasts correlate with the degree of anemia. Hence, Stat5 controls a rate-determining step regulating early erythroblast survival.

  • Ineffective erythropoiesis in Stat5a(-/-)5b(-/-) mice due to decreased survival of early erythroblasts.
    Blood, 2001
    Co-Authors: Merav Socolovsky, Volker H Haase, Carlo Brugnara, Mark D. Fleming, Harvey F. Lodish
    Abstract:

    Erythropoietin (Epo) controls red cell production in the basal state and during stress. Epo binding to its receptor, EpoR, on erythroid progenitors leads to rapid activation of the transcription factor Stat5. Previously, fetal anemia and increased apoptosis of fetal liver erythroid progenitors were found in Stat5a−/−5b−/− mice. However, the role of Stat5 in adult erythropoiesis was not clear. The present study shows that some adult Stat5a−/−5b−/− mice have a near-normal hematocrit but are deficient in generating high erythropoietic rates in response to stress. Further, many adult Stat5a−/−5b−/− mice have persistent anemia despite a marked compensatory expansion in their erythropoietic tissue. Analysis of erythroblast maturation in Stat5a−/−5b−/− hematopoietic tissue shows a dramatic increase in early erythroblast numbers, but these fail to progress in differentiation. Decreased expression of bcl-xLand increased apoptosis in Stat5a−/−5b−/−early erythroblasts correlate with the degree of anemia. Hence, Stat5 controls a rate-determining step regulating early erythroblast survival.