Einzeltreffer — DigiBib

The balance between hematopoietic progenitor commitment and self-renewal versus differentiation is controlled by various transcriptional regulators cooperating with cytokine receptors. Disruption of this balance is increasingly recognized as important in the development of leukemia, by causing enhanced renewal and differentiation arrest. We studied regulation of renewal versus differentiation in primary murine erythroid progenitors that require cooperation of erythropoietin receptor (EpoR), the receptor tyrosine kinase c-Kit and a transcriptional regulator (glucocorticoid receptor; GR) for sustained renewal. However, mice defective for GR- (GR(dim/dim)), EpoR- (EpoR(H)) or STAT5ab function (Stat5ab(-/-)) show no severe erythropoiesis defects in vivo. Using primary erythroblast cultures from these mutants, we present genetic evidence that functional GR, EpoR, and Stat5 are essential for erythroblast renewal in vitro. Cells from GR(dim/dim), EpoR(H), and Stat5ab(-/-) mice showed enhanced differentiation instead of renewal, causing accumulation of mature cells and gradual proliferation arrest. Stat5ab was additionally required for Epo-induced terminal differentiation: differentiating Stat5ab(-/-) erythroblasts underwent apoptosis instead of erythrocyte maturation, due to absent induction of the antiapoptotic protein Bcl-X(L). This defect could be fully rescued by exogenous Bcl-X(L). These data suggest that signaling molecules driving leukemic proliferation may also be essential for prolonged self-renewal of normal erythroid progenitors.

Titel:	Erythroid progenitor renewal versus differentiation: genetic evidence for cell autonomous, essential functions of EpoR, Stat5 and the GR.
Autor/in / Beteiligte Person:	Dolznig, H ; Grebien, F ; Deiner, EM ; Stangl, K ; Kolbus, A ; Habermann, B ; Kerenyi, MA ; Kieslinger, M ; Moriggl, R ; Beug, H ; Müllner, EW
Link:	Volltext (PDF)
Zeitschrift:	Oncogene, Jg. 25 (2006-05-11), Heft 20, S. 2890-900
Veröffentlichung:	<2002->: Basingstoke : Nature Publishing Group ; <i>Original Publication</i>: Basingstoke, Hampshire, UK : Scientific & Medical Division, MacMillan Press, c1987-, 2006
Medientyp:	academicJournal
ISSN:	0950-9232 (print)
DOI:	10.1038/sj.onc.1209308
Schlagwort:	Animals Apoptosis Blotting, Western Cells, Cultured Embryo, Mammalian cytology Embryo, Mammalian metabolism Erythroblasts cytology Erythroblasts metabolism Flow Cytometry Humans Liver cytology Liver metabolism Mice bcl-X Protein genetics bcl-X Protein metabolism Cell Differentiation Cell Proliferation Erythroid Precursor Cells metabolism Receptors, Erythropoietin physiology Receptors, Glucocorticoid physiology STAT5 Transcription Factor physiology
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article; Research Support, Non-U.S. Gov't Language: English [Oncogene] 2006 May 11; Vol. 25 (20), pp. 2890-900. MeSH Terms: Cell Differentiation* ; Cell Proliferation* ; Erythroid Precursor Cells / metabolism ; Receptors, Erythropoietin / physiology ; Receptors, Glucocorticoid / physiology ; STAT5 Transcription Factor / physiology ; Animals ; Apoptosis ; Blotting, Western ; Cells, Cultured ; Embryo, Mammalian / cytology ; Embryo, Mammalian / metabolism ; Erythroblasts / cytology ; Erythroblasts / metabolism ; Flow Cytometry ; Humans ; Liver / cytology ; Liver / metabolism ; Mice ; bcl-X Protein / genetics ; bcl-X Protein / metabolism References: Mol Cell Biol. 2004 Sep;24(18):8037-47. (PMID: 15340066) ; J Cell Physiol. 1990 Feb;142(2):219-30. (PMID: 2154501) ; Nat Rev Cancer. 2003 Sep;3(9):650-65. (PMID: 12951584) ; Blood. 2004 Sep 15;104(6):1873-80. (PMID: 15166028) ; J Biol Chem. 1999 Aug 6;274(32):22165-9. (PMID: 10428780) ; Blood. 1999 Jul 15;94(2):550-9. (PMID: 10397722) ; Oncogene. 2001 Jun 21;20(28):3651-64. (PMID: 11439328) ; Genes Dev. 1995 Jul 1;9(13):1608-21. (PMID: 7628695) ; EMBO J. 2001 Jun 15;20(12):3156-66. (PMID: 11406592) ; Nat Rev Cancer. 2004 Feb;4(2):97-105. (PMID: 14964307) ; Nature. 1995 Sep 21;377(6546):242-6. (PMID: 7545788) ; Genes Dev. 1998 Aug 15;12(16):2475-87. (PMID: 9716401) ; Cancer Cell. 2005 Jan;7(1):87-99. (PMID: 15652752) ; Cell. 2001 Jun 29;105(7):829-41. (PMID: 11439179) ; Adv Exp Med Biol. 2000;480:139-46. (PMID: 10959420) ; Curr Biol. 2002 Jul 9;12(13):1076-85. (PMID: 12121614) ; Mol Cell Biol. 1996 Oct;16(10):5691-700. (PMID: 8816482) ; Oncogene. 1999 Jul 22;18(29):4191-9. (PMID: 10435632) ; Cell Growth Differ. 1995 Nov;6(11):1341-52. (PMID: 8562472) ; J Exp Med. 1999 Jun 7;189(11):1691-8. (PMID: 10359572) ; Cell. 1998 May 1;93(3):385-95. (PMID: 9590173) ; J Exp Med. 2002 Nov 18;196(10):1347-53. (PMID: 12438425) ; Nat Rev Cancer. 2005 Mar;5(3):172-83. (PMID: 15719031) ; EMBO J. 2002 Aug 15;21(16):4297-306. (PMID: 12169632) ; Genes Dev. 2000 Jan 15;14(2):232-44. (PMID: 10652277) ; Mol Cell Biol. 1998 Oct;18(10):5852-60. (PMID: 9742102) ; Oncogene. 1995 Jul 6;11(1):59-72. (PMID: 7624132) ; Cell. 1999 Jul 23;98(2):181-91. (PMID: 10428030) ; Blood. 1997 Aug 15;90(4):1345-64. (PMID: 9269751) ; Nat Rev Cancer. 2003 Feb;3(2):89-101. (PMID: 12563308) ; Science. 1997 Nov 14;278(5341):1309-12. (PMID: 9360930) ; Blood. 1996 Sep 1;88(5):1576-82. (PMID: 8781412) ; Nucleic Acids Res. 1995 Jun 25;23(12):2342-3. (PMID: 7610066) ; Nat Rev Cancer. 2003 Dec;3(12):895-902. (PMID: 14737120) ; Nat Genet. 1998 Feb;18(2):126-35. (PMID: 9462740) ; Exp Hematol. 2005 Feb;33(2):182-8. (PMID: 15676212) ; Cell Cycle. 2004 Jul;3(7):876-9. (PMID: 15254422) ; Methods Mol Med. 2005;105:323-44. (PMID: 15492405) ; Blood. 2003 Nov 1;102(9):3147-53. (PMID: 12869513) ; Cell. 1998 May 29;93(5):841-50. (PMID: 9630227) ; Leukemia. 2002 Aug;16(8):1402-11. (PMID: 12145676) ; Genes Dev. 1999 Nov 15;13(22):2996-3002. (PMID: 10580006) ; FASEB J. 2001 Jun;15(8):1442-4. (PMID: 11387251) ; Cell. 1998 May 15;93(4):531-41. (PMID: 9604929) ; Cell. 1998 May 1;93(3):397-409. (PMID: 9590174) ; Mol Cell. 2000 Sep;6(3):693-704. (PMID: 11030348) ; Biochim Biophys Acta. 1996 Dec 9;1288(3):M35-47. (PMID: 9011180) Grant Information: F 2801 Austria FWF_ Austrian Science Fund FWF; F 2802 Austria FWF_ Austrian Science Fund FWF; F 2807 Austria FWF_ Austrian Science Fund FWF; F 2809 Austria FWF_ Austrian Science Fund FWF Contributed Indexing: Indexing Agency: NLM Local ID #: UKMS32172. Substance Nomenclature: 0 (Receptors, Erythropoietin) ; 0 (Receptors, Glucocorticoid) ; 0 (STAT5 Transcription Factor) ; 0 (bcl-X Protein) Entry Date(s): Date Created: 20060113 Date Completed: 20060620 Latest Revision: 20240314 Update Code: 20240314 PubMed Central ID: PMC3035873

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Erythroid progenitor renewal versus differentiation: genetic evidence for cell autonomous, essential functions of EpoR, Stat5 and the GR.