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EBF1 is essential for B-Lineage priming and establishment of a transcription factor network in common lymphoid progenitors

Zandi, Sasan; Månsson, Robert LU ; Tsapogas, Panagiotis; Zetterblad, Jenny; Bryder, David LU and Sigvardsson, Mikael LU (2008) In Journal of Immunology 181(5). p.3364-3372
Abstract
Development of B-lymphoid cells in the bone marrow is a process under strict control of a hierarchy of transcription factors. To understand the development of a B-lymphoid-restricted functional network of transcription factors, we have investigated the cell autonomous role of the transcription factor EBF1 in early B cell development. This revealed that even though transplanted EBF1-deficient fetal liver cells were able to generate common lymphoid progenitors (CLPs) as well as B220(+)CD43(+)AA4.1(+) candidate precursor B cells, none of these populations showed signs of B lineage priming. The isolated CLPs were able to generate T lymphocytes in vitro supporting the idea that the phenotype of EBF1-deficient mice is restricted to the... (More)
Development of B-lymphoid cells in the bone marrow is a process under strict control of a hierarchy of transcription factors. To understand the development of a B-lymphoid-restricted functional network of transcription factors, we have investigated the cell autonomous role of the transcription factor EBF1 in early B cell development. This revealed that even though transplanted EBF1-deficient fetal liver cells were able to generate common lymphoid progenitors (CLPs) as well as B220(+)CD43(+)AA4.1(+) candidate precursor B cells, none of these populations showed signs of B lineage priming. The isolated CLPs were able to generate T lymphocytes in vitro supporting the idea that the phenotype of EBF1-deficient mice is restricted to the development of the B lineage. Furthermore, EBF deficient CLPs displayed a reduction in Ig H chain recombination as compared with their wild-type counterpart and essentially lacked transcription of B-lineage-associated genes. Among the genes displaying reduced expression in the EBF1 deficient CLPs were the transcription factors Pax5, Pou2af1 (OcaB), and FoxO1 that all appear to be direct genetic targets for EBF1 because their promoters contained functional binding sites for this factor. This leads us to suggest that EBF1 regulates a transcription factor network crucial for B lineage commitment. (Less)
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author
organization
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Contribution to journal
publication status
published
subject
in
Journal of Immunology
volume
181
issue
5
pages
3364 - 3372
publisher
American Association of Immunologists
external identifiers
  • wos:000259511800046
  • scopus:51549083884
ISSN
1550-6606
language
English
LU publication?
yes
id
b6289e62-2adb-4b56-9ce8-71a737d99e3c (old id 1287252)
alternative location
http://www.jimmunol.org/cgi/reprint/181/5/3364
date added to LUP
2009-01-28 09:33:35
date last changed
2017-06-25 04:13:09
@article{b6289e62-2adb-4b56-9ce8-71a737d99e3c,
  abstract     = {Development of B-lymphoid cells in the bone marrow is a process under strict control of a hierarchy of transcription factors. To understand the development of a B-lymphoid-restricted functional network of transcription factors, we have investigated the cell autonomous role of the transcription factor EBF1 in early B cell development. This revealed that even though transplanted EBF1-deficient fetal liver cells were able to generate common lymphoid progenitors (CLPs) as well as B220(+)CD43(+)AA4.1(+) candidate precursor B cells, none of these populations showed signs of B lineage priming. The isolated CLPs were able to generate T lymphocytes in vitro supporting the idea that the phenotype of EBF1-deficient mice is restricted to the development of the B lineage. Furthermore, EBF deficient CLPs displayed a reduction in Ig H chain recombination as compared with their wild-type counterpart and essentially lacked transcription of B-lineage-associated genes. Among the genes displaying reduced expression in the EBF1 deficient CLPs were the transcription factors Pax5, Pou2af1 (OcaB), and FoxO1 that all appear to be direct genetic targets for EBF1 because their promoters contained functional binding sites for this factor. This leads us to suggest that EBF1 regulates a transcription factor network crucial for B lineage commitment.},
  author       = {Zandi, Sasan and Månsson, Robert and Tsapogas, Panagiotis and Zetterblad, Jenny and Bryder, David and Sigvardsson, Mikael},
  issn         = {1550-6606},
  language     = {eng},
  number       = {5},
  pages        = {3364--3372},
  publisher    = {American Association of Immunologists},
  series       = {Journal of Immunology},
  title        = {EBF1 is essential for B-Lineage priming and establishment of a transcription factor network in common lymphoid progenitors},
  volume       = {181},
  year         = {2008},
}