spacer gif spacer gif spacer gif spacer gif spacer gif
QUICK SEARCH:   [advanced]


spacer gif
     Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents    

This Article
Right arrow Figures Only
Right arrow Full Text
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 Email this article to a friend
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 reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Sánchez, M.-J.
Right arrow Articles by Green, A. R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Sánchez, M.-J.
Right arrow Articles by Green, A. R.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?
Development 128, 4815-4827 (2001)
© 2001 The Company of Biologists Limited

Selective rescue of early haematopoietic progenitors in Scl–/– mice by expressing Scl under the control of a stem cell enhancer

María-José Sánchez1,*, Ernesto-Otto Bockamp2, Jane Miller1, Laure Gambardella1 and Anthony R. Green1

1 University of Cambridge, Department of Haematology, CIMR Centre, Hills Road, Cambridge CB2 2XY, UK
2 Johannes Gutenberg-University, Institute of Toxicology, Laboratory of Molecular Mouse Genetics, Obere Zahlbacher Str. 67, 55131 Mainz, Germany

*Author for correspondence (e-mail: mss24{at}cus.cam.ac.uk)

Accepted September 10, 2001

The stem cell leukaemia gene (Scl) encodes a basic helix-loop-helix transcription factor with a pivotal role in both haematopoiesis and endothelial development. During mouse development, Scl is first expressed in extra-embryonic mesoderm, and is required for the generation of all haematopoietic lineages and normal yolk sac angiogenesis. Ectopic expression of Scl during zebrafish development specifies haemangioblast formation from early mesoderm. These results suggest that SCL is essential for establishing the transcriptional programme responsible for the formation of haematopoietic stem cells and have focused attention on the transcriptional regulation of Scl itself. Previous studies have identified a panel of Scl enhancers each of which directed expression to a subdomain of the normal Scl expression pattern. Among them, a 3' enhancer directed expression during development to vascular endothelium and haematopoietic progenitors but not to Ter119+ erythroid cells. The expression in haematopoietic stem cells, however, remained undetermined. We demonstrate that this 3' enhancer directs lacZ expression in transgenic mice to most foetal and adult long-term repopulating haematopoietic stem cells, and therefore functions as a stem cell enhancer. Consistent with these results, expression in Scl–/– embryos of exogenous Scl driven by the stem cell enhancer rescued the formation of early haematopoietic progenitors and also resulted in normal yolk sac angiogenesis. By contrast, erythropoiesis remained markedly deficient in rescued embryos. This observation is consistent with the inactivity of the stem cell enhancer in erythroid cells and reveals an essential role for SCL during erythroid differentiation in vivo.

Key words: Scl gene, Stem cell enhancer, Haematopoietic Stem cells, Mouse


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati   Add to Twitter Twitter    What's this?


This article has been cited by other articles:


Home page
 Proc. Natl. Acad. Sci. USAHome page
X. Hu, X. Li, K. Valverde, X. Fu, C. Noguchi, Y. Qiu, and S. Huang
LSD1-mediated epigenetic modification is required for TAL1 function and hematopoiesis
PNAS, June 23, 2009; 106(25): 10141 - 10146.
[Abstract] [Full Text] [PDF]

Home page
 haematolHome page
F. Cerisoli, L. Cassinelli, G. Lamorte, S. Citterio, F. Bertolotti, M. C. Magli, and S. Ottolenghi
Green fluorescent protein transgene driven by Kit regulatory sequences is expressed in hematopoietic stem cells
Haematologica, March 1, 2009; 94(3): 318 - 325.
[Abstract] [Full Text] [PDF]

Home page
 Genome ResHome page
A. M. Smith, M.-J. Sanchez, G. A. Follows, S. Kinston, I. J. Donaldson, A. R. Green, and B. Gottgens
A novel mode of enhancer evolution: The Tal1 stem cell enhancer recruited a MIR element to specifically boost its activity
Genome Res., September 1, 2008; 18(9): 1422 - 1432.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
J. Sausville, A. A. Molinolo, X. Cheng, J. Frampton, N. Takebe, J. S. Gutkind, and R. A. Feldman
RCAS/SCL-TVA Animal Model Allows Targeted Delivery of Polyoma Middle T Oncogene to Vascular Endothelial Progenitors In vivo and Results in Hemangioma Development
Clin. Cancer Res., June 15, 2008; 14(12): 3948 - 3955.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
J. E. Pimanda, K. Ottersbach, K. Knezevic, S. Kinston, W. Y. I. Chan, N. K. Wilson, J.-R. Landry, A. D. Wood, A. Kolb-Kokocinski, A. R. Green, et al.
Gata2, Fli1, and Scl form a recursively wired gene-regulatory circuit during early hematopoietic development
PNAS, November 6, 2007; 104(45): 17692 - 17697.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
S. Ogilvy, R. Ferreira, S. G. Piltz, J. M. Bowen, B. Gottgens, and A. R. Green
The SCL +40 Enhancer Targets the Midbrain Together with Primitive and Definitive Hematopoiesis and Is Regulated by SCL and GATA Proteins
Mol. Cell. Biol., October 15, 2007; 27(20): 7206 - 7219.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
J. E. Pimanda, I. J. Donaldson, M. F. T. R. de Bruijn, S. Kinston, K. Knezevic, L. Huckle, S. Piltz, J.-R. Landry, A. R. Green, D. Tannahill, et al.
The SCL transcriptional network and BMP signaling pathway interact to regulate RUNX1 activity
PNAS, January 16, 2007; 104(3): 840 - 845.
[Abstract] [Full Text] [PDF]

Home page
 Genome ResHome page
G. A. Follows, P. Dhami, B. Gottgens, A. W. Bruce, P. J. Campbell, S. C. Dillon, A. M. Smith, C. Koch, I. J. Donaldson, M. A. Scott, et al.
Identifying gene regulatory elements by genomic microarray mapping of DNaseI hypersensitive sites
Genome Res., October 1, 2006; 16(10): 1310 - 1319.
[Abstract] [Full Text] [PDF]

Home page
 DevelopmentHome page
X. Li, J.-W. Xiong, C. S. Shelley, H. Park, and M. A. Arnaout
The transcription factor ZBP-89 controls generation of the hematopoietic lineage in zebrafish and mouse embryonic stem cells
Development, September 15, 2006; 133(18): 3641 - 3650.
[Abstract] [Full Text] [PDF]

Home page
 Arterioscler. Thromb. Vasc. Bio.Home page
A. Hamik, B. Wang, and M. K. Jain
Transcriptional Regulators of Angiogenesis
Arterioscler Thromb Vasc Biol, September 1, 2006; 26(9): 1936 - 1947.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
E. Bockamp, C. Antunes, M. Maringer, R. Heck, K. Presser, S. Beilke, S. Ohngemach, R. Alt, M. Cross, R. Sprengel, et al.
Tetracycline-controlled transgenic targeting from the SCL locus directs conditional expression to erythrocytes, megakaryocytes, granulocytes, and c-kit-expressing lineage-negative hematopoietic cells
Blood, September 1, 2006; 108(5): 1533 - 1541.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
J. E. Pimanda, L. Silberstein, M. Dominici, B. Dekel, M. Bowen, S. Oldham, A. Kallianpur, S. J. Brandt, D. Tannahill, B. Gottgens, et al.
Transcriptional Link between Blood and Bone: the Stem Cell Leukemia Gene and Its +19 Stem Cell Enhancer Are Active in Bone Cells.
Mol. Cell. Biol., April 1, 2006; 26(7): 2615 - 2625.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
M. A. Juarez, F. Su, S. Chun, M. J. Kiel, and S. E. Lyons
Distinct Roles for SCL in Erythroid Specification and Maturation in Zebrafish
J. Biol. Chem., December 16, 2005; 280(50): 41636 - 41644.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
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., August 1, 2005; 25(15): 6355 - 6362.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
E. Delabesse, S. Ogilvy, M. A. Chapman, S. G. Piltz, B. Gottgens, and A. R. Green
Transcriptional Regulation of the SCL Locus: Identification of an Enhancer That Targets the Primitive Erythroid Lineage In Vivo
Mol. Cell. Biol., June 15, 2005; 25(12): 5215 - 5225.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
J. R. Gothert, S. E. Gustin, M. A. Hall, A. R. Green, B. Gottgens, D. J. Izon, and C. G. Begley
In vivo fate-tracing studies using the Scl stem cell enhancer: embryonic hematopoietic stem cells significantly contribute to adult hematopoiesis
Blood, April 1, 2005; 105(7): 2724 - 2732.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
I. J. Donaldson, M. Chapman, S. Kinston, J. R. Landry, K. Knezevic, S. Piltz, N. Buckley, A. R. Green, and B. Gottgens
Genome-wide identification of cis-regulatory sequences controlling blood and endothelial development
Hum. Mol. Genet., March 1, 2005; 14(5): 595 - 601.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
M. Eguchi, M. Eguchi-Ishimae, A. Green, T. Enver, and M. Greaves
Directing oncogenic fusion genes into stem cells via an SCL enhancer
PNAS, January 25, 2005; 102(4): 1133 - 1138.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
S. Koschmieder, B. Gottgens, P. Zhang, J. Iwasaki-Arai, K. Akashi, J. L. Kutok, T. Dayaram, K. Geary, A. R. Green, D. G. Tenen, et al.
Inducible chronic phase of myeloid leukemia with expansion of hematopoietic stem cells in a transgenic model of BCR-ABL leukemogenesis
Blood, January 1, 2005; 105(1): 324 - 334.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
J. R. Gothert, S. E. Gustin, J. A. M. van Eekelen, U. Schmidt, M. A. Hall, S. M. Jane, A. R. Green, B. Gottgens, D. J. Izon, and C. G. Begley
Genetically tagging endothelial cells in vivo: bone marrow-derived cells do not contribute to tumor endothelium
Blood, September 15, 2004; 104(6): 1769 - 1777.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
M. J. Abeyta, A. T. Clark, R. T. Rodriguez, M. S. Bodnar, R. A. R. Pera, and M. T. Firpo
Unique gene expression signatures of independently-derived human embryonic stem cell lines
Hum. Mol. Genet., March 15, 2004; 13(6): 601 - 608.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
B. Gottgens, C. Broccardo, M.-J. Sanchez, S. Deveaux, G. Murphy, J. R. Gothert, E. Kotsopoulou, S. Kinston, L. Delaney, S. Piltz, et al.
The scl +18/19 Stem Cell Enhancer Is Not Required for Hematopoiesis: Identification of a 5' Bifunctional Hematopoietic-Endothelial Enhancer Bound by Fli-1 and Elf-1
Mol. Cell. Biol., March 1, 2004; 24(5): 1870 - 1883.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
R. Lahlil, E. Lecuyer, S. Herblot, and T. Hoang
SCL Assembles a Multifactorial Complex That Determines Glycophorin A Expression
Mol. Cell. Biol., February 15, 2004; 24(4): 1439 - 1452.
[Abstract] [Full Text] [PDF]

Home page
 Genome ResHome page
M. A. Chapman, I. J. Donaldson, J. Gilbert, D. Grafham, J. Rogers, A. R. Green, and B. Gottgens
Analysis of Multiple Genomic Sequence Alignments: A Web Resource, Online Tools, and Lessons Learned From Analysis of Mammalian SCL Loci
Genome Res., February 1, 2004; 14(2): 313 - 318.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
L. A. Cairns, E. Moroni, E. Levantini, A. Giorgetti, F. G. Klinger, S. Ronzoni, L. Tatangelo, C. Tiveron, M. De Felici, S. Dolci, et al.
Kit regulatory elements required for expression in developing hematopoietic and germ cell lineages
Blood, December 1, 2003; 102(12): 3954 - 3962.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
Z. Xu, S. Huang, L.-S. Chang, A. D. Agulnick, and S. J. Brandt
Identification of a TAL1 Target Gene Reveals a Positive Role for the LIM Domain-Binding Protein Ldb1 in Erythroid Gene Expression and Differentiation
Mol. Cell. Biol., November 1, 2003; 23(21): 7585 - 7599.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
G. J. Murphy, B. Gottgens, A. Vegiopoulos, M.-J. Sanchez, A. D. Leavitt, S. P. Watson, A. R. Green, and J. Frampton
Manipulation of Mouse Hematopoietic Progenitors by Specific Retroviral Infection
J. Biol. Chem., October 31, 2003; 278(44): 43556 - 43563.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
M. A. Hall, D. J. Curtis, D. Metcalf, A. G. Elefanty, K. Sourris, L. Robb, J. R. Gothert, S. M. Jane, and C. G. Begley
The critical regulator of embryonic hematopoiesis, SCL, is vital in the adult for megakaryopoiesis, erythropoiesis, and lineage choice in CFU-S12
PNAS, February 4, 2003; 100(3): 992 - 997.
[Abstract] [Full Text] [PDF]

Home page
 Physiol. GenomicsHome page
E. Bockamp, M. Maringer, C. Spangenberg, S. Fees, S. Fraser, L. Eshkind, F. Oesch, and B. Zabel
Of mice and models: improved animal models for biomedical research
Physiol Genomics, December 3, 2002; 11(3): 115 - 132.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
C.-Z. Chen, M. Li, D. de Graaf, S. Monti, B. Gottgens, M.-J. Sanchez, E. S. Lander, T. R. Golub, A. R. Green, and H. F. Lodish
Identification of endoglin as a functional marker that defines long-term repopulating hematopoietic stem cells
PNAS, November 26, 2002; 99(24): 15468 - 15473.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
A. M. Sinclair, A. J. Bench, A. J. C. Bloor, J. Li, B. Gottgens, M. L. Stanley, J. Miller, S. Piltz, S. Hunter, E. P. Nacheva, et al.
Rescue of the lethal scl-/- phenotype by the human SCL locus
Blood, May 13, 2002; 99(11): 3931 - 3938.
[Abstract] [Full Text] [PDF]


© The Company of Biologists Ltd 2001