Article

MLLT3 regulates early human erythroid and megakaryocytic cell fate.

MRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, UK.
Cell stem cell (impact factor: 23.56). 04/2008; 2(3):264-73. DOI:10.1016/j.stem.2008.01.013 pp.264-73
Source: PubMed

ABSTRACT Regulatory mechanisms of human hematopoiesis remain largely uncharacterized. Through expression profiling of prospectively isolated stem and primitive progenitor cells as well as committed progenitors from cord blood (CB), we identified MLLT3 as a candidate regulator of erythroid/megakaryocytic (E/Meg) lineage decisions. Through the analysis of the hematopoietic potential of primitive cord blood cells in which MLLT3 expression has been knocked down, we identify a requirement for MLLT3 in the elaboration of the erythroid and megakaryocytic lineages. Conversely, forced expression of MLLT3 promotes the output of erythroid and megakaryocytic progenitors, and analysis of MLLT3 mutants suggests that this capacity of MLLT3 depends on its transcriptional regulatory activity. Gene expression and cis-regulatory element analyses reveal crossregulatory interactions between MLLT3 and E/Meg-affiliated transcription factor GATA-1. Taken together, the data identify MLLT3 as a regulator of early erythroid and megakaryocytic cell fate in the human system.

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Keywords

candidate regulator
 
cis-regulatory element analyses
 
cord blood
 
crossregulatory interactions
 
E/Meg-affiliated transcription factor GATA-1
 
expression profiling
 
hematopoietic potential
 
human hematopoiesis
 
human system
 
megakaryocytic cell fate
 
megakaryocytic lineages
 
megakaryocytic progenitors
 
MLLT3 expression
 
MLLT3 mutants
 
MLLT3 promotes
 
primitive cord blood cells
 
primitive progenitor cells
 
progenitors
 
Regulatory mechanisms
 
transcriptional regulatory activity