Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
Br J Haematol. 2011 Feb;152(4):469-84. doi: 10.1111/j.1365-2141.2010.08548.x. Epub 2011 Jan 12.

The aryl hydrocarbon receptor (AHR) transcription factor regulates megakaryocytic polyploidization.

Author information

  • 1Department of Chemical Engineering and Delaware Biotechnology Institute, University of Delaware, Newark, DE 19711, USA. slindsey@udel.edu

Abstract

We propose that the aryl hydrocarbon receptor (AHR) is a novel transcriptional regulator of megakaryopoietic polyploidization. Functional evidence was obtained that AHR impacts in vivo megakaryocytic differentiation and maturation; compared to wild-type mice, AHR-null mice had lower platelet counts, fewer numbers of newly synthesized platelets, increased bleeding times and lower-ploidy megakaryocytes (Mks). AHR mRNA increased 3·6-fold during ex vivo megakaryocytic differentiation, but reduced or remained constant during parallel isogenic granulocytic or erythroid differentiation. We interrogated the role of AHR in megakaryopoiesis using a validated Mk model of megakaryopoiesis, the human megakaryoblastic leukaemia CHRF cell line. Upon CHRF Mk differentiation, AHR mRNA and protein levels increased, AHR protein shifted from the cytoplasm to the nucleus and AHR binding to its consensus DNA binding sequence increased. Protein and mRNA levels of the AHR transcriptional target HES1 also increased. Mk differentiation of CHRF cells where AHR or HES1 was knocked-down using RNAi resulted in lower ploidy distributions and cells that were incapable of reaching ploidy classes ≥16n. AHR knockdown also resulted in increased DNA synthesis of lower ploidy cells, without impacting apoptosis. Together, these data support a role for AHR in Mk polyploidization and in vivo platelet function, and warrant further detailed investigations.

© 2011 Blackwell Publishing Ltd.

PMID:
21226706
[PubMed - indexed for MEDLINE]
PMCID:
PMC3408620
Free PMC Article

Images from this publication.See all images (8)Free text

Fig 1
Fig 2
Fig 3
Fig 4
Fig 5
Fig 6
Fig 7
Fig 8
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Blackwell Publishing Icon for PubMed Central
    Loading ...
    Write to the Help Desk