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Blood, 1 December 2001, Vol. 98, No. 12, pp. 3261-3273
HEMATOPOIESIS
Ineffective erythropoiesis in
Stat5a / 5b / mice due to
decreased survival of early erythroblasts
Merav Socolovsky,
Hyung-song Nam,
Mark D. Fleming,
Volker H. Haase,
Carlo Brugnara, and
Harvey F. Lodish
From the Whitehead Institute for Biomedical Research
and Department of Biology, Massachusetts Institute of Technology,
Cambridge, MA; Department of Pathology, Children's Hospital;
Department of Laboratory Medicine, Children's Hospital, Harvard
Medical School; Renal Division, Beth Israel Deaconess Medical Center
and Harvard Medical School, Boston, MA.
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-xL
and increased apoptosis in Stat5a / 5b /
early erythroblasts correlate with the degree of anemia. Hence, Stat5
controls a rate-determining step regulating early erythroblast survival.

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The locus control region is required for association of the murine beta-globin locus with engaged transcription factories during erythroid maturation
Genes & Dev.,
June 1, 2006;
20(11):
1447 - 1457.
[Abstract]
[Full Text]
[PDF]
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B. Li, N. Jia, R. Kapur, and K. T. Chun
Cul4A targets p27 for degradation and regulates proliferation, cell cycle exit, and differentiation during erythropoiesis
Blood,
June 1, 2006;
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[Abstract]
[Full Text]
[PDF]
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T. Katsumoto, Y. Aikawa, A. Iwama, S. Ueda, H. Ichikawa, T. Ochiya, and I. Kitabayashi
MOZ is essential for maintenance of hematopoietic stem cells.
Genes & Dev.,
May 15, 2006;
20(10):
1321 - 1330.
[Abstract]
[Full Text]
[PDF]
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H. M. Rooke and S. H. Orkin
Phosphorylation of Gata1 at serine residues 72, 142, and 310 is not essential for hematopoiesis in vivo
Blood,
May 1, 2006;
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3527 - 3530.
[Abstract]
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K. Wagner, P. Zhang, F. Rosenbauer, B. Drescher, S. Kobayashi, H. S. Radomska, J. L. Kutok, D. G. Gilliland, J. Krauter, and D. G. Tenen
Absence of the transcription factor CCAAT enhancer binding protein {alpha} results in loss of myeloid identity in bcr/abl-induced malignancy
PNAS,
April 18, 2006;
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[Abstract]
[Full Text]
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T. Ito, N. Arimitsu, M. Takeuchi, N. Kawamura, M. Nagata, K. Saso, N. Akimitsu, H. Hamamoto, S. Natori, A. Miyajima, et al.
Transcription Elongation Factor S-II Is Required for Definitive Hematopoiesis
Mol. Cell. Biol.,
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[Abstract]
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M. P. Menon, J. Fang, and D. M. Wojchowski
Core erythropoietin receptor signals for late erythroblast development
Blood,
April 1, 2006;
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[Abstract]
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M. Um and H. F. Lodish
Antiapoptotic Effects of Erythropoietin in Differentiated Neuroblastoma SH-SY5Y Cells Require Activation of Both the STAT5 and AKT Signaling Pathways
J. Biol. Chem.,
March 3, 2006;
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[Abstract]
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A. D. Patterson, M. C. Hollander, G. F. Miller, and A. J. Fornace Jr.
Gadd34 requirement for normal hemoglobin synthesis.
Mol. Cell. Biol.,
March 1, 2006;
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[Abstract]
[Full Text]
[PDF]
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J. F. Langenheim, D. Tan, A. M. Walker, and W. Y. Chen
Two Wrongs Can Make a Right: Dimers of Prolactin and Growth Hormone Receptor Antagonists Behave as Agonists
Mol. Endocrinol.,
March 1, 2006;
20(3):
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[Abstract]
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K. Kitajima, M. Tanaka, J. Zheng, H. Yen, A. Sato, D. Sugiyama, H. Umehara, E. Sakai, and T. Nakano
Redirecting differentiation of hematopoietic progenitors by a transcription factor, GATA-2
Blood,
March 1, 2006;
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[Abstract]
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M. Sanchez, I. L. Weissman, M. Pallavicini, M. Valeri, P. Guglielmelli, A. M. Vannucchi, G. Migliaccio, and A. R. Migliaccio
Differential Amplification of Murine Bipotent Megakaryocytic/Erythroid Progenitor and Precursor Cells During Recovery from Acute and Chronic Erythroid Stress
Stem Cells,
February 1, 2006;
24(2):
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[Abstract]
[Full Text]
[PDF]
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J. M. Brown, J. Leach, J. E. Reittie, A. Atzberger, J. Lee-Prudhoe, W. G. Wood, D. R. Higgs, F. J. Iborra, and V. J. Buckle
Coregulated human globin genes are frequently in spatial proximity when active
J. Cell Biol.,
January 17, 2006;
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[Abstract]
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J. Zheng, K. Kitajima, E. Sakai, T. Kimura, N. Minegishi, M. Yamamoto, and T. Nakano
Differential effects of GATA-1 on proliferation and differentiation of erythroid lineage cells
Blood,
January 15, 2006;
107(2):
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[Abstract]
[Full Text]
[PDF]
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T. Ishikawa-Sekigami, Y. Kaneko, H. Okazawa, T. Tomizawa, J. Okajo, Y. Saito, C. Okuzawa, M. Sugawara-Yokoo, U. Nishiyama, H. Ohnishi, et al.
SHPS-1 promotes the survival of circulating erythrocytes through inhibition of phagocytosis by splenic macrophages
Blood,
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[Abstract]
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[PDF]
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F. Martelli, B. Ghinassi, B. Panetta, E. Alfani, V. Gatta, A. Pancrazzi, C. Bogani, A. M. Vannucchi, F. Paoletti, G. Migliaccio, et al.
Variegation of the phenotype induced by the Gata1low mutation in mice of different genetic backgrounds
Blood,
December 15, 2005;
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[Abstract]
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C. J. Wu, L. Krishnamurti, J. L. Kutok, M. Biernacki, S. Rogers, W. Zhang, J. H. Antin, and J. Ritz
Evidence for ineffective erythropoiesis in severe sickle cell disease
Blood,
November 15, 2005;
106(10):
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[Abstract]
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L. Silberstein, M.-J. Sanchez, M. Socolovsky, Y. Liu, G. Hoffman, S. Kinston, S. Piltz, M. Bowen, L. Gambardella, A. R. Green, et al.
Transgenic Analysis of the Stem Cell Leukemia +19 Stem Cell Enhancer in Adult and Embryonic Hematopoietic and Endothelial Cells
Stem Cells,
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[Abstract]
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M. M. Rhodes, P. Kopsombut, M. C. Bondurant, J. O. Price, and M. J. Koury
Bcl-xL prevents apoptosis of late-stage erythroblasts but does not mediate the antiapoptotic effect of erythropoietin
Blood,
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106(5):
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[Abstract]
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M. A. Hall, N. J. Slater, C. G. Begley, J. M. Salmon, L. J. Van Stekelenburg, M. P. McCormack, S. M. Jane, and D. J. Curtis
Functional but Abnormal Adult Erythropoiesis in the Absence of the Stem Cell Leukemia Gene
Mol. Cell. Biol.,
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M. Pesu, J. O'Shea, L. Hennighausen, and O. Silvennoinen
Identification of an Acquired Mutation in Jak2 Provides Molecular Insights into the Pathogenesis of Myeloproliferative Disorders
Mol. Interv.,
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[Abstract]
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W. Tong, J. Zhang, and H. F. Lodish
Lnk inhibits erythropoiesis and Epo-dependent JAK2 activation and downstream signaling pathways
Blood,
June 15, 2005;
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[Abstract]
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R. Doyonnas, J. S. Nielsen, S. Chelliah, E. Drew, T. Hara, A. Miyajima, and K. M. McNagny
Podocalyxin is a CD34-related marker of murine hematopoietic stem cells and embryonic erythroid cells
Blood,
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[Abstract]
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C. Angelin-Duclos, C. Domenget, A. Kolbus, H. Beug, P. Jurdic, and J. Samarut
Thyroid hormone T3 acting through the thyroid hormone {alpha} receptor is necessary for implementation of erythropoiesis in the neonatal spleen environment in the mouse
Development,
March 1, 2005;
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[Abstract]
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G. Terszowski, C. Waskow, P. Conradt, D. Lenze, J. Koenigsmann, D. Carstanjen, I. Horak, and H.-R. Rodewald
Prospective isolation and global gene expression analysis of the erythrocyte colony-forming unit (CFU-E)
Blood,
March 1, 2005;
105(5):
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[Abstract]
[Full Text]
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A. L. Drayer, A.-K. Boer, E. L. Los, M. T. Esselink, and E. Vellenga
Stem Cell Factor Synergistically Enhances Thrombopoietin-Induced STAT5 Signaling in Megakaryocyte Progenitors through JAK2 and Src Kinase
Stem Cells,
February 1, 2005;
23(2):
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[Abstract]
[Full Text]
[PDF]
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A. Halupa, M. L. Bailey, K. Huang, N. N. Iscove, D. E. Levy, and D. L. Barber
A novel role for STAT1 in regulating murine erythropoiesis: deletion of STAT1 results in overall reduction of erythroid progenitors and alters their distribution
Blood,
January 15, 2005;
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[Abstract]
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M. Nakano, K. Ohneda, H. Yamamoto-Mukai, R. Shimizu, O. Ohneda, S. Ohmura, M. Suzuki, S. Tsukamoto, T. Yanagawa, H. Yoshida, et al.
Transgenic over-expression of GATA-1 mutant lacking N-finger domain causes hemolytic syndrome in mouse erythroid cells
Genes Cells,
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[Abstract]
[Full Text]
[PDF]
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K. W. Harder, C. Quilici, E. Naik, M. Inglese, N. Kountouri, A. Turner, K. Zlatic, D. M. Tarlinton, and M. L. Hibbs
Perturbed myelo/erythropoiesis in Lyn-deficient mice is similar to that in mice lacking the inhibitory phosphatases SHP-1 and SHIP-1
Blood,
December 15, 2004;
104(13):
3901 - 3910.
[Abstract]
[Full Text]
[PDF]
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Y. Nakano, S. Imagawa, K. Matsumoto, C. Stockmann, N. Obara, N. Suzuki, T. Doi, T. Kodama, S. Takahashi, T. Nagasawa, et al.
Oral administration of K-11706 inhibits GATA binding activity, enhances hypoxia-inducible factor 1 binding activity, and restores indicators in an in vivo mouse model of anemia of chronic disease
Blood,
December 15, 2004;
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4300 - 4307.
[Abstract]
[Full Text]
[PDF]
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J. J. Schuringa, K. Wu, G. Morrone, and M. A.S. Moore
Enforced Activation of STAT5A Facilitates the Generation of Embryonic Stem-Derived Hematopoietic Stem Cells That Contribute to Hematopoiesis In Vivo
Stem Cells,
December 1, 2004;
22(7):
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[Abstract]
[Full Text]
[PDF]
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Y. Cui, G. Riedlinger, K. Miyoshi, W. Tang, C. Li, C.-X. Deng, G. W. Robinson, and L. Hennighausen
Inactivation of Stat5 in Mouse Mammary Epithelium during Pregnancy Reveals Distinct Functions in Cell Proliferation, Survival, and Differentiation
Mol. Cell. Biol.,
September 15, 2004;
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[Abstract]
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C. Waskow, G. Terszowski, C. Costa, M. Gassmann, and H.-R. Rodewald
Rescue of lethal c-KitW/W mice by erythropoietin
Blood,
September 15, 2004;
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[Abstract]
[Full Text]
[PDF]
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J. J. Schuringa, K. Y. Chung, G. Morrone, and M. A.S. Moore
Constitutive Activation of STAT5A Promotes Human Hematopoietic Stem Cell Self-Renewal and Erythroid Differentiation
J. Exp. Med.,
September 7, 2004;
200(5):
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R. M. Teague, R. M. Tempero, S. Thomas, K. Murali-Krishna, and B. H. Nelson
Proliferation and Differentiation of CD8+ T Cells in the Absence of IL-2/15 Receptor {beta}-Chain Expression or STAT5 Activation
J. Immunol.,
September 1, 2004;
173(5):
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[Abstract]
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S. M. Jacobs-Helber and S. T. Sawyer
Jun N-terminal kinase promotes proliferation of immature erythroid cells and erythropoietin-dependent cell lines
Blood,
August 1, 2004;
104(3):
696 - 703.
[Abstract]
[Full Text]
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W. Zhou, Q. Zhao, R. Sutton, H. Cumming, X. Wang, L. Cerruti, M. Hall, R. Wu, J. M. Cunningham, and S. M. Jane
The Role of p22 NF-E4 in Human Globin Gene Switching
J. Biol. Chem.,
June 18, 2004;
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[Abstract]
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E. van den Akker, T. van Dijk, M. Parren-van Amelsvoort, K. S. Grossmann, U. Schaeper, K. Toney-Earley, S. E. Waltz, B. Lowenberg, and M. von Lindern
Tyrosine kinase receptor RON functions downstream of the erythropoietin receptor to induce expansion of erythroid progenitors
Blood,
June 15, 2004;
103(12):
4457 - 4465.
[Abstract]
[Full Text]
[PDF]
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K.-H. Chang, M. Tam, and M. M. Stevenson
Inappropriately low reticulocytosis in severe malarial anemia correlates with suppression in the development of late erythroid precursors
Blood,
May 15, 2004;
103(10):
3727 - 3735.
[Abstract]
[Full Text]
[PDF]
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H. Beauchemin, M.-J. Blouin, and M. Trudel
Differential Regulatory and Compensatory Responses in Hematopoiesis/Erythropoiesis in {alpha}- and {beta}-Globin Hemizygous Mice
J. Biol. Chem.,
May 7, 2004;
279(19):
19471 - 19480.
[Abstract]
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