Abstract |
Pbx1, a homeodomain transcription factor that was originally identified as the product of a proto-oncogene in acute pre-B-cell leukemia, is a global regulator of embryonic development. However, embryonic lethality in its absence has prevented an assessment of its role in B-cell development. Here, using Rag1-deficient blastocyst complementation assays, we demonstrate that Pbx1 null embryonic stem (ES) cells fail to generate common lymphoid progenitors (CLPs) resulting in a complete lack of B and NK cells, and a partial impairment of T-cell development in chimeric mice. A critical role for Pbx1 was confirmed by rescue of B-cell development from CLPs following restoration of its expression in Pbx1-deficient ES cells. In adoptive transfer experiments, B-cell development from Pbx1-deficient fetal liver cells was also severely compromised, but not erased, since transient B lymphopoiesis was detected in Rag-deficient recipients. Conditional inactivation of Pbx1 in pro-B (CD19(+)) cells and thereafter revealed that Pbx1 is not necessary for B-cell development to proceed from the pro-B-cell stage. Thus, Pbx1 critically functions at a stage between hematopoietic stem cell development and B-cell commitment and, therefore, is one of the earliest-acting transcription factors that regulate de novo B-lineage lymphopoiesis.
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Authors | Mrinmoy Sanyal, James W Tung, Holger Karsunky, Hong Zeng, Licia Selleri, Irving L Weissman, Leonore A Herzenberg, Michael L Cleary |
Journal | Blood
(Blood)
Vol. 109
Issue 10
Pg. 4191-9
(May 15 2007)
ISSN: 0006-4971 [Print] United States |
PMID | 17244677
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- Homeodomain Proteins
- Pbx1 protein, mouse
- Pre-B-Cell Leukemia Transcription Factor 1
- Transcription Factors
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Topics |
- Animals
- B-Lymphocytes
(cytology)
- Blastocyst
(immunology)
- Chimera
(genetics)
- Gene Expression Regulation, Developmental
- Genes, RAG-1
- Hematopoietic Stem Cells
(cytology)
- Homeodomain Proteins
(genetics)
- Liver
(cytology, embryology)
- Lymphopoiesis
(genetics)
- Mice
- Mice, Inbred C57BL
- Mice, Knockout
- Pre-B-Cell Leukemia Transcription Factor 1
- Transcription Factors
(genetics)
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