Abstract
Commitment towards megakaryocyte versus erythroid blood cell lineages occurs in the megakaryocyte-erythroid progenitor, where mutually exclusive expression of either EKLF (Klf1) or Fli1 defines alternative outcomes. Here we show there is a marked increase in the number of circulating platelets in mice lacking the erythroid transcription factor EKLF. In addition, committed erythroid cells retain key signatures of megakaryocytes both on the cell surface and at the mRNA level. We also show that the effect of EKLF on megakaryocyte-erythroid progenitor lineage decision and commitment is cell autonomous in bone marrow reconstitution assays where stem cells lacking EKLF favor the megakaryocyte differentiation pathway. We conclude the megakaryocyte program is aberrantly activated in EKLF null erythroid cells.
MeSH Terms
Animals
Bone Marrow Cells/cytology,metabolism
Cell Differentiation/genetics
Cell Lineage/genetics
Kruppel-Like Transcription Factors/blood,deficiency,genetics
Megakaryocyte-Erythroid Progenitor Cells/cytology,metabolism
Mice
Mice, Inbred BALB C
Mice, Knockout
Mice, Transgenic
Chemicals
Kruppel-Like Transcription Factors
erythroid Kruppel-like factor
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Tallack Michael R
Institute for Molecular Bioscience, University of Queensland, St Lucia, 4072 Qld, Australia.
Perkins Andrew C
References (17)
17 references, click to expand
-
Erythroid Kruppel-like factor (EKLF) coordinates erythroid cell proliferation and hemoglobinization in cell lines derived from EKLF null mice.
Blood. 2001 Mar 15;97(6):1861-8
PMID: 11238130
-
EKLF restricts megakaryocytic differentiation at the benefit of erythrocytic differentiation.
Blood. 2008 Aug 1;112(3):576-84
PMID: 18523154
-
Sumoylation of EKLF promotes transcriptional repression and is involved in inhibition of megakaryopoiesis.
Mol Cell Biol. 2007 Dec;27(24):8547-60
PMID: 17938210
-
Activation of Eklf expression during hematopoiesis by Gata2 and Smad5 prior to erythroid commitment.
Development. 2008 Jun;135(12):2071-82
PMID: 18448565
-
Novel role for EKLF in megakaryocyte lineage commitment.
Blood. 2007 Dec 1;110(12):3871-80
PMID: 17715392
-
Fli-1 is required for murine vascular and megakaryocytic development and is hemizygously deleted in patients with thrombocytopenia.
Immunity. 2000 Aug;13(2):167-77
PMID: 10981960
-
Functional cross-antagonism between transcription factors FLI-1 and EKLF.
Mol Cell Biol. 2003 Feb;23(4):1390-402
PMID: 12556498
-
Lethal beta-thalassaemia in mice lacking the erythroid CACCC-transcription factor EKLF.
Nature. 1995 May 25;375(6529):318-22
PMID: 7753195
-
The erythroid phenotype of EKLF-null mice: defects in hemoglobin metabolism and membrane stability.
Mol Cell Biol. 2005 Jun;25(12):5205-14
PMID: 15923635
-
Erythroid Krüppel-like factor directly activates the basic Krüppel-like factor gene in erythroid cells.
Mol Cell Biol. 2007 Apr;27(7):2777-90
PMID: 17283065
-
A novel, erythroid cell-specific murine transcription factor that binds to the CACCC element and is related to the Krüppel family of nuclear proteins.
Mol Cell Biol. 1993 May;13(5):2776-86
PMID: 7682653
-
Defective haematopoiesis in fetal liver resulting from inactivation of the EKLF gene.
Nature. 1995 May 25;375(6529):316-8
PMID: 7753194
-
Sp1 and krüppel-like factor family of transcription factors in cell growth regulation and cancer.
J Cell Physiol. 2001 Aug;188(2):143-60
PMID: 11424081
-
'Green mice' as a source of ubiquitous green cells.
FEBS Lett. 1997 May 5;407(3):313-9
PMID: 9175875
-
The megakaryocyte lineage originates from hemangioblast precursors and is an integral component both of primitive and of definitive hematopoiesis.
Blood. 2007 Feb 15;109(4):1433-41
PMID: 17062726
-
A global role for EKLF in definitive and primitive erythropoiesis.
Blood. 2006 Apr 15;107(8):3359-70
PMID: 16380451
-
Maturation stage-specific regulation of megakaryopoiesis by pointed-domain Ets proteins.
Blood. 2006 Oct 1;108(7):2198-206
PMID: 16757682