Transcription factor EBF restricts alternative lineage options and promotes B cell fate commitment independently of Pax5

Jagan M R Pongubala, Daniel L. Northrup, David W. Lancki, Kay L Medina, Thomas Treiber, Eric Bertolino, Matthew Thomas, Rudolf Grosschedl, David Allman, Harinder Singh

Research output: Contribution to journalArticle

174 Citations (Scopus)

Abstract

Alternative lineage restriction and B cell fate commitment require the transcription factor Pax5, but the function of early B cell factor (EBF) in these processes remains mostly unexplored. Here we show that in the absence of EBF, 'expandable' and clonal lymphoid progenitor cells retained considerable myeloid potential. Conversely, ectopic expression of EBF in multipotential progenitor cells directed B cell generation at the expense of myeloid cell fates. EBF induced Pax5 and antagonized expression of genes encoding the transcription factors C/EBPα, PU.1 and Id2. Notably, sustained expression of EBF in Pax5 -/- hematopoietic progenitor cells was sufficient to block their myeloid and T lineage potential in vivo. Furthermore, in Pax5 -/- pro-B cells, higher EBF expression repressed alternative lineage genes. Thus, EBF can restrict alternative lineage 'choice' and promote commitment to the B cell fate independently of Pax5.

Original languageEnglish (US)
Pages (from-to)203-215
Number of pages13
JournalNature Immunology
Volume9
Issue number2
DOIs
StatePublished - Feb 2008

Fingerprint

B-Lymphocytes
Transcription Factors
Lymphoid Progenitor Cells
3'-(1-butylphosphoryl)adenosine
B-Lymphoid Precursor Cells
Myeloid Cells
Hematopoietic Stem Cells
Stem Cells
Gene Expression
Genes

ASJC Scopus subject areas

  • Immunology

Cite this

Pongubala, J. M. R., Northrup, D. L., Lancki, D. W., Medina, K. L., Treiber, T., Bertolino, E., ... Singh, H. (2008). Transcription factor EBF restricts alternative lineage options and promotes B cell fate commitment independently of Pax5. Nature Immunology, 9(2), 203-215. https://doi.org/10.1038/ni1555

Transcription factor EBF restricts alternative lineage options and promotes B cell fate commitment independently of Pax5. / Pongubala, Jagan M R; Northrup, Daniel L.; Lancki, David W.; Medina, Kay L; Treiber, Thomas; Bertolino, Eric; Thomas, Matthew; Grosschedl, Rudolf; Allman, David; Singh, Harinder.

In: Nature Immunology, Vol. 9, No. 2, 02.2008, p. 203-215.

Research output: Contribution to journalArticle

Pongubala, JMR, Northrup, DL, Lancki, DW, Medina, KL, Treiber, T, Bertolino, E, Thomas, M, Grosschedl, R, Allman, D & Singh, H 2008, 'Transcription factor EBF restricts alternative lineage options and promotes B cell fate commitment independently of Pax5', Nature Immunology, vol. 9, no. 2, pp. 203-215. https://doi.org/10.1038/ni1555
Pongubala, Jagan M R ; Northrup, Daniel L. ; Lancki, David W. ; Medina, Kay L ; Treiber, Thomas ; Bertolino, Eric ; Thomas, Matthew ; Grosschedl, Rudolf ; Allman, David ; Singh, Harinder. / Transcription factor EBF restricts alternative lineage options and promotes B cell fate commitment independently of Pax5. In: Nature Immunology. 2008 ; Vol. 9, No. 2. pp. 203-215.
@article{370b709a09034dbfac2d24805df13fec,
title = "Transcription factor EBF restricts alternative lineage options and promotes B cell fate commitment independently of Pax5",
abstract = "Alternative lineage restriction and B cell fate commitment require the transcription factor Pax5, but the function of early B cell factor (EBF) in these processes remains mostly unexplored. Here we show that in the absence of EBF, 'expandable' and clonal lymphoid progenitor cells retained considerable myeloid potential. Conversely, ectopic expression of EBF in multipotential progenitor cells directed B cell generation at the expense of myeloid cell fates. EBF induced Pax5 and antagonized expression of genes encoding the transcription factors C/EBPα, PU.1 and Id2. Notably, sustained expression of EBF in Pax5 -/- hematopoietic progenitor cells was sufficient to block their myeloid and T lineage potential in vivo. Furthermore, in Pax5 -/- pro-B cells, higher EBF expression repressed alternative lineage genes. Thus, EBF can restrict alternative lineage 'choice' and promote commitment to the B cell fate independently of Pax5.",
author = "Pongubala, {Jagan M R} and Northrup, {Daniel L.} and Lancki, {David W.} and Medina, {Kay L} and Thomas Treiber and Eric Bertolino and Matthew Thomas and Rudolf Grosschedl and David Allman and Harinder Singh",
year = "2008",
month = "2",
doi = "10.1038/ni1555",
language = "English (US)",
volume = "9",
pages = "203--215",
journal = "Nature Immunology",
issn = "1529-2908",
publisher = "Nature Publishing Group",
number = "2",

}

TY - JOUR

T1 - Transcription factor EBF restricts alternative lineage options and promotes B cell fate commitment independently of Pax5

AU - Pongubala, Jagan M R

AU - Northrup, Daniel L.

AU - Lancki, David W.

AU - Medina, Kay L

AU - Treiber, Thomas

AU - Bertolino, Eric

AU - Thomas, Matthew

AU - Grosschedl, Rudolf

AU - Allman, David

AU - Singh, Harinder

PY - 2008/2

Y1 - 2008/2

N2 - Alternative lineage restriction and B cell fate commitment require the transcription factor Pax5, but the function of early B cell factor (EBF) in these processes remains mostly unexplored. Here we show that in the absence of EBF, 'expandable' and clonal lymphoid progenitor cells retained considerable myeloid potential. Conversely, ectopic expression of EBF in multipotential progenitor cells directed B cell generation at the expense of myeloid cell fates. EBF induced Pax5 and antagonized expression of genes encoding the transcription factors C/EBPα, PU.1 and Id2. Notably, sustained expression of EBF in Pax5 -/- hematopoietic progenitor cells was sufficient to block their myeloid and T lineage potential in vivo. Furthermore, in Pax5 -/- pro-B cells, higher EBF expression repressed alternative lineage genes. Thus, EBF can restrict alternative lineage 'choice' and promote commitment to the B cell fate independently of Pax5.

AB - Alternative lineage restriction and B cell fate commitment require the transcription factor Pax5, but the function of early B cell factor (EBF) in these processes remains mostly unexplored. Here we show that in the absence of EBF, 'expandable' and clonal lymphoid progenitor cells retained considerable myeloid potential. Conversely, ectopic expression of EBF in multipotential progenitor cells directed B cell generation at the expense of myeloid cell fates. EBF induced Pax5 and antagonized expression of genes encoding the transcription factors C/EBPα, PU.1 and Id2. Notably, sustained expression of EBF in Pax5 -/- hematopoietic progenitor cells was sufficient to block their myeloid and T lineage potential in vivo. Furthermore, in Pax5 -/- pro-B cells, higher EBF expression repressed alternative lineage genes. Thus, EBF can restrict alternative lineage 'choice' and promote commitment to the B cell fate independently of Pax5.

UR - http://www.scopus.com/inward/record.url?scp=38449102306&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=38449102306&partnerID=8YFLogxK

U2 - 10.1038/ni1555

DO - 10.1038/ni1555

M3 - Article

C2 - 18176567

AN - SCOPUS:38449102306

VL - 9

SP - 203

EP - 215

JO - Nature Immunology

JF - Nature Immunology

SN - 1529-2908

IS - 2

ER -