PMID- 17923245
OWN - NLM
STAT- MEDLINE
DCOM- 20080304
LR  - 20071224
IS  - 0301-472X (Print)
IS  - 0301-472X (Linking)
VI  - 36
IP  - 1
DP  - 2008 Jan
TI  - NF-E2-mediated enhancement of megakaryocytic differentiation and platelet 
      production in vitro and in vivo.
PG  - 78-92
AB  - OBJECTIVE: NF-E2 is a prime regulator of megakaryocyte (MK) terminal 
      differentiation and platelet release. By overexpressing the p45 subunit of NF-E2, 
      we aim to increase the proportion of mature MKs and the potential for platelet 
      production in vitro and in vivo. METHODS: Retroviral vectors expressing p45-NF-E2 
      together with the enhanced green fluorescent protein (eGFP) were used to 
      transduce murine bone marrow cells (BMCs). Aspects of MK differentiation, 
      proliferation, proplatelet, and platelet production were evaluated. RESULTS: 
      Compared to controls, a higher proportion of BMCs overexpressing p45-NF-E2 were 
      found to express the MK markers CD41, CD42a, and CD42b, with some effect on cell 
      proliferation. Early MK differentiation, characterized by colony-forming unit 
      (CFU)-MK formation, was enhanced by p45-NF-E2 overexpression at the expense of 
      CFU-granulocyte macrophage development. An increased number of 
      acetylcholinesterase(+) MKs was also observed in NF-E2(++) cultures. Although 
      endomitosis was found not to be affected, the resultant upregulation of NF-E2 
      target genes was also followed by significant increases in proplatelet and 
      functional platelet production. Transplantation of enriched MK progenitor cells 
      overexpressing p45-NF-E2 into lethally irradiated mice resulted in a threefold 
      increase in eGFP(+)/NF-E2(++) platelet production in vivo over 10 days, although 
      no appreciable expansion in their number was observed over 32 days. CONCLUSION: 
      These results suggest that enforced expression of p45-NF-E2 selectively enhances 
      many aspects of MK differentiation, including MK maturation, proplatelet 
      formation, and platelet release. In addition, p45 overexpression increases MK 
      commitment during early megakaryopoiesis, while inhibiting white blood cell 
      differentiation.
FAU - Fock, Ee-ling
AU  - Fock EL
AD  - Centre for Vascular Research, Department of Medicine, St. George Clinical School, 
      University of New South Wales, Sydney, Australia.
FAU - Yan, Feng
AU  - Yan F
FAU - Pan, Shu
AU  - Pan S
FAU - Chong, Beng H
AU  - Chong BH
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20071017
PL  - Netherlands
TA  - Exp Hematol
JT  - Experimental hematology
JID - 0402313
RN  - 0 (NF-E2 Transcription Factor, p45 Subunit)
RN  - 0 (Recombinant Fusion Proteins)
RN  - EC 3.1.1.7 (Acetylcholinesterase)
SB  - IM
MH  - Acetylcholinesterase/biosynthesis/genetics
MH  - Animals
MH  - Blood Platelets/*cytology
MH  - Bone Marrow Cells/*cytology
MH  - Cell Differentiation
MH  - Cells, Cultured/cytology
MH  - Colony-Forming Units Assay
MH  - Enzyme Induction
MH  - Granulocytes/cytology
MH  - Hematopoietic Stem Cell Transplantation
MH  - Megakaryocytes/*cytology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Myelopoiesis
MH  - NF-E2 Transcription Factor, p45 Subunit/genetics/*physiology
MH  - Ploidies
MH  - Radiation Chimera
MH  - Recombinant Fusion Proteins/physiology
MH  - Thrombopoiesis/*physiology
MH  - Transduction, Genetic
EDAT- 2007/10/10 09:00
MHDA- 2008/03/05 09:00
CRDT- 2007/10/10 09:00
PHST- 2007/04/19 00:00 [received]
PHST- 2007/08/07 00:00 [revised]
PHST- 2007/08/09 00:00 [accepted]
PHST- 2007/10/10 09:00 [pubmed]
PHST- 2008/03/05 09:00 [medline]
PHST- 2007/10/10 09:00 [entrez]
AID - S0301-472X(07)00523-1 [pii]
AID - 10.1016/j.exphem.2007.08.015 [doi]
PST - ppublish
SO  - Exp Hematol. 2008 Jan;36(1):78-92. doi: 10.1016/j.exphem.2007.08.015. Epub 2007 
      Oct 17.