Intrinsic and extrinsic effects of mafG deficiency on hematopoietic recovery following bone marrow transplant.
OBJECTIVE
MafG is the small subunit of the transcription factor NF-E2 that controls terminal megakaryocyte maturation and platelet release. Studies were conducted to evaluate the intrinsic and extrinsic effects of mafG deficiency on bone marrow engraftment kinetics.


METHODS
We used mafG knockout mice either as donors or recipients in bone marrow transplantations with wild-type mice and compared the engraftment kinetics to transplantations using wild-type donors and recipients. We measured peripheral cell counts, the presence of circulating donor-derived cells by flow cytometry, changes in the cellularity of the bone marrow and splenic weight on day 5, 7, 14, and 1 month post-transplantation.


RESULTS
Compared to wild-type recipients, mafG recipients had delayed platelet and leukocyte recovery and lower spleen weight at early time points after transplantation. Intrinsic effects: When mafG-deficient bone marrow served as donor source, we observed more rapid recovery of bone marrow cellularity and increased splenic hematopoiesis. The finding of increased short-term hematopoietic stem cells and progenitors in the mafG-deficient bone marrow could explain the accelerated hematopoietic recovery after transplantation. Furthermore, the expression of Bach 2, which can form a heterodimer with mafG protein, was found to be greatly reduced, while Notch 1 expression was increased in mafG-deficient mice. Extrinsic effects: When mafG-deficient mice were transplant recipients, there were delays in recovery of normal levels of marrow and splenic hematopoiesis as well as circulating leukocytes and platelets.


CONCLUSIONS
Our study demonstrates that mafG expression has intrinsic and extrinsic effects on hematopoietic engraftment following bone marrow transplantation.
Li
Xiao-Miao
XM
Department of Pediatrics, University of Florida, Gainesville, FL 32610, USA.
Hu
Zhongbo
Z
Zafar
Abu-Bakr
AB
Jorgensen
Marda L
ML
Bungert
Jorg
J
Slayton
William
W
D000818:Animals; D050976:Basic-Leucine Zipper Transcription Factors / Q000032:analysis; D016026:Bone Marrow Transplantation; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000166:cytology; D007958:Leukocyte Count; D051259:MafG Transcription Factor / Q000172:deficiency / Q000502:physiology*; D008533:Megakaryocytes / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D010976:Platelet Count; D051881:Receptor, Notch1 / Q000032:analysis; D012097:Repressor Proteins / Q000172:deficiency / Q000502:physiology*; D013154:Spleen / Q000166:cytology
C102109:Bach2 protein, mouse; D050976:Basic-Leucine Zipper Transcription Factors; D051259:MafG Transcription Factor; C491247:Mafg protein, mouse; C497762:Notch1 protein, mouse; D051881:Receptor, Notch1; D012097:Repressor Proteins