Assembling a gene regulatory network for specification of the B cell fate

Kay L Medina, Jagan M R Pongubala, Karen L. Reddy, David W. Lancki, Rodney DeKoter, Matthias Kieslinger, Rudolf Grosschedl, Harinder Singh

Research output: Contribution to journalArticle

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Abstract

The generation of B lymphocyte precursors is dependent on the combinatorial action of the transcription factors PU.1, Ikaros, E2A, EBF, and Pax-5. Loss of PU.1 results in a severe reduction in Flk2+, IL-7R+ lymphoid progenitors as well as impaired expression of EBF and Pax-5. Restoration of EBF expression facilitates rapid generation of pro-B cells from PU.1-/- progenitors. Molecular analysis suggests that PU.1 directly participates in regulation of the EBF gene. Although PU.1 is dispensable for expression of most early B lineage genes, it is required for CD45R/B220. Using EBF-/- mutant progenitors, we show that EBF induces Pax-5 and the early program of B lineage gene expression. Importantly, Pax-5 does not rescue B cell development from either PU.1-/- or EBF-/- progenitors. Pax-5 expression and function are contingent on EBF. Based on these results, we propose a hierarchical regulatory network for specification and commitment to the B cell fate.

Original languageEnglish (US)
Pages (from-to)607-617
Number of pages11
JournalDevelopmental Cell
Volume7
Issue number4
DOIs
StatePublished - Oct 2004
Externally publishedYes

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B-Lymphoid Precursor Cells
Gene Regulatory Networks
B-Lymphocytes
Genes
Cells
Specifications
Transcription Factors
Lymphocytes
Gene Expression
Gene expression
Restoration

ASJC Scopus subject areas

  • Developmental Biology

Cite this

Medina, K. L., Pongubala, J. M. R., Reddy, K. L., Lancki, D. W., DeKoter, R., Kieslinger, M., ... Singh, H. (2004). Assembling a gene regulatory network for specification of the B cell fate. Developmental Cell, 7(4), 607-617. https://doi.org/10.1016/j.devcel.2004.08.006

Assembling a gene regulatory network for specification of the B cell fate. / Medina, Kay L; Pongubala, Jagan M R; Reddy, Karen L.; Lancki, David W.; DeKoter, Rodney; Kieslinger, Matthias; Grosschedl, Rudolf; Singh, Harinder.

In: Developmental Cell, Vol. 7, No. 4, 10.2004, p. 607-617.

Research output: Contribution to journalArticle

Medina, KL, Pongubala, JMR, Reddy, KL, Lancki, DW, DeKoter, R, Kieslinger, M, Grosschedl, R & Singh, H 2004, 'Assembling a gene regulatory network for specification of the B cell fate', Developmental Cell, vol. 7, no. 4, pp. 607-617. https://doi.org/10.1016/j.devcel.2004.08.006
Medina KL, Pongubala JMR, Reddy KL, Lancki DW, DeKoter R, Kieslinger M et al. Assembling a gene regulatory network for specification of the B cell fate. Developmental Cell. 2004 Oct;7(4):607-617. https://doi.org/10.1016/j.devcel.2004.08.006
Medina, Kay L ; Pongubala, Jagan M R ; Reddy, Karen L. ; Lancki, David W. ; DeKoter, Rodney ; Kieslinger, Matthias ; Grosschedl, Rudolf ; Singh, Harinder. / Assembling a gene regulatory network for specification of the B cell fate. In: Developmental Cell. 2004 ; Vol. 7, No. 4. pp. 607-617.
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