CG&D
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cell Growth & Differentiation

This Article
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Dolznig, H.
Right arrow Articles by Beug, H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Dolznig, H.
Right arrow Articles by Beug, H.

Cell Growth & Differentiation, Vol 6, Issue 11 1341-1352, Copyright © 1995 by American Association of Cancer Research


ARTICLES

Terminal differentiation of normal chicken erythroid progenitors: shortening of G1 correlates with loss of D-cyclin/cdk4 expression and altered cell size control

H Dolznig, P Bartunek, K Nasmyth, EW Mullner and H Beug
Institute of Molecular Pathology, Vienna Biocenter, Austria.

Detailed knowledge is available about the molecular makeup of the cell cycle clock in dividing cells. However, comparatively little is known about cell cycle regulation during terminal differentiation. Here we describe a primary cell system in which this question can be addressed. Normal avian erythroid progenitors undergo continuous self-renewal in suspension culture in the presence of growth factors and hormones, allowing us to obtain large cell numbers (10(10)-10(11)). By replacing these "self-renewal factors" with erythropoietin and insulin, the cells can be induced to synchronous, terminal differentiation. During the first 72 h, the cells undergo five cell divisions. Thereafter, they arrest in G1 and complete their maturation into RBC without further divisions. Sixteen to 24 h after induction of differentiation, the cell cycle length decreased from about 20 to 12 h. This shortened doubling time was due to a drastic reduction of G1 (from 12 to 5 h), while S- and G2-phase lengths were not affected. At the same time, the differentiating cells underwent an extensive and concerted switch in their gene expression pattern. During the subsequent four cell divisions, the cell volume decreased from about 300 to less than 70 femtoliters, but the rate of protein synthesis normalized to cell volume remained constant. Interestingly, the shortening of G1 was accompanied by a rapid down-regulation of D-type cyclins and their partner, cyclin-dependent kinase type 4 (cdk4), while expression of S- and G2-M-associated cell cycle regulators (cyclin A and cdk1/cdc2) remained high until the cells arrested in G1 72-96 h after differentiation induction. We conclude that concerted reprogramming of progenitor gene expression during erythroid differentiation is accompanied by profoundly altered cell cycle progression involving the loss or alteration of cell size control at the restriction point.


This article has been cited by other articles:


Home page
haematolHome page
I. Z. Uras, R. M. Scheicher, K. Kollmann, M. Glosmann, M. Prchal-Murphy, A. S. Tigan, D. A. Fux, S. Altamura, J. Neves, M. U. Muckenthaler, et al.
Cdk6 contributes to cytoskeletal stability in erythroid cells
Haematologica, June 1, 2017; 102(6): 995 - 1005.
[Abstract] [Full Text] [PDF]


Home page
haematolHome page
S. R. Jayapal, C. Q. Wang, X. Bisteau, M. J. Caldez, S. Lim, V. Tergaonkar, M. Osato, and P. Kaldis
Hematopoiesis specific loss of Cdk2 and Cdk4 results in increased erythrocyte size and delayed platelet recovery following stress
Haematologica, April 1, 2015; 100(4): 431 - 438.
[Abstract] [Full Text] [PDF]


Home page
BloodHome page
X. Li-Harms, S. Milasta, J. Lynch, C. Wright, A. Joshi, R. Iyengar, G. Neale, X. Wang, Y.-D. Wang, T. A. Prolla, et al.
Mito-protective autophagy is impaired in erythroid cells of aged mtDNA-mutator mice
Blood, January 1, 2015; 125(1): 162 - 174.
[Abstract] [Full Text] [PDF]


Home page
ASH Education BookHome page
M. J. Koury and M. Rhodes
How to approach chronic anemia
Hematology, December 1, 2012; 2012(1): 183 - 190.
[Abstract] [Full Text] [PDF]


Home page
Genes Dev.Home page
V. G. Sankaran, L. S. Ludwig, E. Sicinska, J. Xu, D. E. Bauer, J. C. Eng, H. C. Patterson, R. A. Metcalf, Y. Natkunam, S. H. Orkin, et al.
Cyclin D3 coordinates the cell cycle during differentiation to regulate erythrocyte size and number
Genes & Dev., September 15, 2012; 26(18): 2075 - 2087.
[Abstract] [Full Text] [PDF]


Home page
BloodHome page
J. Fang, M. Menon, W. Kapelle, O. Bogacheva, O. Bogachev, E. Houde, S. Browne, P. Sathyanarayana, and D. M. Wojchowski
EPO modulation of cell-cycle regulatory genes, and cell division, in primary bone marrow erythroblasts
Blood, October 1, 2007; 110(7): 2361 - 2370.
[Abstract] [Full Text] [PDF]


Home page
JEMHome page
C. G. Leung, Y. Xu, B. Mularski, H. Liu, S. Gurbuxani, and J. D. Crispino
Requirements for survivin in terminal differentiation of erythroid cells and maintenance of hematopoietic stem and progenitor cells
J. Exp. Med., July 9, 2007; 204(7): 1603 - 1611.
[Abstract] [Full Text] [PDF]


Home page
BloodHome page
M. von Lindern
Cell-cycle control in erythropoiesis
Blood, August 1, 2006; 108(3): 781 - 782.
[Full Text] [PDF]


Home page
BloodHome page
C. Leberbauer, F. Boulme, G. Unfried, J. Huber, H. Beug, and E. W. Mullner
Different steroids co-regulate long-term expansion versus terminal differentiation in primary human erythroid progenitors
Blood, January 1, 2005; 105(1): 85 - 94.
[Abstract] [Full Text] [PDF]


Home page
J Biol ChemHome page
W. Aerbajinai, Y. T. Lee, U. Wojda, V. A. Barr, and J. L. Miller
Cloning and Characterization of a Gene Expressed during Terminal Differentiation That Encodes a Novel Inhibitor of Growth
J. Biol. Chem., January 16, 2004; 279(3): 1916 - 1921.
[Abstract] [Full Text] [PDF]


Home page
BloodHome page
A. Kolbus, M. Blazquez-Domingo, S. Carotta, W. Bakker, S. Luedemann, M. von Lindern, P. Steinlein, and H. Beug
Cooperative signaling between cytokine receptors and the glucocorticoid receptor in the expansion of erythroid progenitors: molecular analysis by expression profiling
Blood, November 1, 2003; 102(9): 3136 - 3146.
[Abstract] [Full Text] [PDF]


Home page
Mol. Cell. Biol.Home page
M. Rylski, J. J. Welch, Y.-Y. Chen, D. L. Letting, J. A. Diehl, L. A. Chodosh, G. A. Blobel, and M. J. Weiss
GATA-1-Mediated Proliferation Arrest during Erythroid Maturation
Mol. Cell. Biol., July 15, 2003; 23(14): 5031 - 5042.
[Abstract] [Full Text] [PDF]


Home page
J. Immunol.Home page
J. F. Modiano, J. Mayor, C. Ball, M. K. Fuentes, and D. S. Linthicum
CDK4 Expression and Activity Are Required for Cytokine Responsiveness in T Cells
J. Immunol., December 15, 2000; 165(12): 6693 - 6702.
[Abstract] [Full Text] [PDF]


Home page
BloodHome page
M.-S. Dai, C. R. Mantel, Z.-B. Xia, H. E. Broxmeyer, and L. Lu
An expansion phase precedes terminal erythroid differentiation of hematopoietic progenitor cells from cord blood in vitro and is associated with up-regulation of cyclin E and cyclin-dependent kinase 2
Blood, December 1, 2000; 96(12): 3985 - 3987.
[Abstract] [Full Text] [PDF]


Home page
J Biol ChemHome page
M. von Lindern, M. P.-v. Amelsvoort, T. van Dijk, E. Deiner, E. van den Akker, S. van Emst-de Vries, P. Willems, H. Beug, and B. Lowenberg
Protein Kinase C {alpha} Controls Erythropoietin Receptor Signaling
J. Biol. Chem., November 3, 2000; 275(44): 34719 - 34727.
[Abstract] [Full Text] [PDF]


Home page
BloodHome page
W. Mikulits, M. Schranzhofer, A. Bauer, H. Dolznig, L. Lobmayr, A. A. Infante, H. Beug, and E. W. Mullner
Impaired Ferritin mRNA Translation in Primary Erythroid Progenitors: Shift to Iron-Dependent Regulation by the v-ErbA Oncoprotein
Blood, December 15, 1999; 94(12): 4321 - 4332.
[Abstract] [Full Text] [PDF]


Home page
Mol. Biol. CellHome page
Z. H. Lu, H. Xu, and G. H. Leno
DNA Replication in Quiescent Cell Nuclei: Regulation by the Nuclear Envelope and Chromatin Structure
Mol. Biol. Cell, December 1, 1999; 10(12): 4091 - 4106.
[Abstract] [Full Text]


Home page
BloodHome page
M. von Lindern, W. Zauner, G. Mellitzer, P. Steinlein, G. Fritsch, K. Huber, B. Lowenberg, and H. Beug
The Glucocorticoid Receptor Cooperates With the Erythropoietin Receptor and c-Kit to Enhance and Sustain Proliferation of Erythroid Progenitors In Vitro
Blood, July 15, 1999; 94(2): 550 - 559.
[Abstract] [Full Text] [PDF]


Home page
Mol. Cell. Biol.Home page
A. Tamir, J. Howard, R. R. Higgins, Y.-J. Li, L. Berger, E. Zacksenhaus, M. Reis, and Y. Ben-David
Fli-1, an Ets-Related Transcription Factor, Regulates Erythropoietin-Induced Erythroid Proliferation and Differentiation: Evidence for Direct Transcriptional Repression of the Rb Gene during Differentiation
Mol. Cell. Biol., June 1, 1999; 19(6): 4452 - 4464.
[Abstract] [Full Text] [PDF]


Home page
EMBO J.Home page
O. Gandrillon, U. Schmidt, H. Beug, and J. Samarut
TGF-{beta} cooperates with TGF-{alpha} to induce the self-renewal of normal erythrocytic progenitors: evidence for an autocrine mechanism
EMBO J., May 17, 1999; 18(10): 2764 - 2781.
[Abstract] [Full Text] [PDF]


Home page
EMBO J.Home page
P. Ciana, G. G. Braliou, F. G. Demay, M. von Lindern, D. Barettino, H. Beug, and H. G. Stunnenberg
Leukemic transformation by the v-ErbA oncoprotein entails constitutive binding to and repression of an erythroid enhancer in vivo
EMBO J., December 15, 1998; 17(24): 7382 - 7394.
[Abstract] [Full Text] [PDF]


Home page
BloodHome page
B. Panzenbock, P. Bartunek, M. Y. Mapara, and M. Zenke
Growth and Differentiation of Human Stem Cell Factor/Erythropoietin-Dependent Erythroid Progenitor Cells In Vitro
Blood, November 15, 1998; 92(10): 3658 - 3668.
[Abstract] [Full Text] [PDF]


Home page
EMBO J.Home page
A. Bauer, W. Mikulits, G. Lagger, G. Stengl, G. Brosch, and H. Beug
The thyroid hormone receptor functions as a ligand-operated developmental switch between proliferation and differentiation of erythroid progenitors
EMBO J., August 3, 1998; 17(15): 4291 - 4303.
[Abstract] [Full Text] [PDF]


Home page
JCBHome page
O. Wessely, E.-M. Deiner, K. C. Lim, G. Mellitzer, P. Steinlein, and H. Beug
Mammalian Granulocyte-Macrophage Colony-stimulating Factor Receptor Expressed in Primary Avian Hematopoietic Progenitors: Lineage-specific Regulation of Proliferation and Differentiation
J. Cell Biol., May 18, 1998; 141(4): 1041 - 1051.
[Abstract] [Full Text] [PDF]


Home page
EMBO J.Home page
O. Wessely, E.-M. Deiner, H. Beug, and M. von Lindern
The glucocorticoid receptor is a key regulator of the decision between self-renewal and differentiation in erythroid progenitors
EMBO J., January 15, 1997; 16(2): 267 - 280.
[Abstract] [Full Text] [PDF]


Home page
J Biol ChemHome page
M. von Lindern, M. P.-v. Amelsvoort, T. van Dijk, E. Deiner, E. van den Akker, S. van Emst-de Vries, P. Willems, H. Beug, and B. Lowenberg
Protein Kinase C {alpha} Controls Erythropoietin Receptor Signaling
J. Biol. Chem., November 3, 2000; 275(44): 34719 - 34727.
[Abstract] [Full Text] [PDF]




HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cell Growth & Differentiation
Copyright © 1995 by the American Association of Cancer Research.